SU1212324A3 - Method of producing tetrazole derivatives or their pharmaceutically acceptable acid-additive salts - Google Patents

Abstract

A process for preparing tetrazole derivatives of the general formula N-N iS JLsiOrA-Wm-Ri x-. where R is hydrogen, C, -C-alkyl, phenyl - or Cj-Cg-cycloalkyl; X is a carbonyl group of an iy group -5- (0) „; and p O or 1 or 2; ha O or 1; And - With, - With - alksh1en; R, -Ch-C-alkyl, C-C3-cycloalkyl naphth1-w, a group of the formula -C (NH) NHRj (where R is C, -C-alkyl-phenylalkyl, in which alkyl has 1-6 carbon atoms and in which phenyl core can be substituted with halogen, phenyl containing J-3 substituents from among halogen, C, -C, C (-C-alkyl, C, -C-alkoxyl, C-C-alkanoyl ananine, -alkyl, substituted by heterocyclic a group which may have a substituent selected from among Cf-alkyl or an amino group, where the heterocrypt group is selected from pyridyl, furyl, thiazolc, a heterocyclic group with 1-4 heteroatoms. - from among nitrogen, oxygen or sulfur, which may have 1-2 substituents from among C -Cg-alkyl, halogen, carboxyl, oxo, amino, C -C-apcoxycarbonyl, hydroxyl, amino, nitro, phenyl, cycloalkyl or C-C-alkylamino, and in the case when m "O, R, may also be a group of the formula -NR3R4 where RJ is hydrogen. C, -Cj-alkyl or phenyl (C, -C) alkyl; R4 hydrogen C -Cg-alkyl, the group -CZNHRj ;, where Z is sulfur or an amino group which may be substituted with C, -C-alxyl; Ry is C-Cj-alkyl or an amino group, or tetrazolyl, which may be substituted with C, -Cg-alkyl or a group -N-CO-RJ, where Rg is C-C-alkyl, phenyl, which may have 1-3 substituents among C -Cj-alkoxyl, Cj-Cg-cycloapkyl, or R 5- or 6-membered unsaturated nitrogen or sulfur-containing heterocycle, or R and RJ together with the common nitrogen atom form a group (L

Description

with the proviso that when V 1 or 2, then m "I and X is sulfur, or their pharmacologically acceptable acid addition salts, characterized in that the tetrazole of the general formula

Nn

I 1

N

where R has the indicated meanings;

Z, group Y. (where

Y, halogen,

mercapto or amidinogroup), or Z. — the -S- (0) .- AY group, in which A, f, and Y have the indicated meanings, is reacted with a compound of the formula Zj-Yj, where Yj is a mercapto or the amidino group in the case when Y is halogen, and Zg is a group A- (X) -R, (where A, X, di and R have the indicated meanings), and when Z, Y, sh Z 2 is a group R then

Z is the group - S (0) j-A-Y, in the presence of a hydrogen halide acceptor at a temperature of from room temperature to a period of time from 30 to 6 hours, followed by isolation of the desired product as a base or acid addition salt.

Priority featured

01.03. 80 R - C —C-alkyl, phenyl, or C5-Cd-cycloalksh1; R, - C, -C5-alkyl, phenyl, C, -C-cycloalkyl, a pyriday heterocyclic group, substituted or unsubstituted thiazolyl, or tetrazolyl, or when

1212324

m О, then R, 4 is the group -IfRjR, where RJ is hydrogen, C, -C-alkyl, coxycarboyl, or R) and R together with the common nitrogen atom form a group

a O or 1; f 0; X is sulfur; A, Z, Z, Y and Yj are all values.

09.16.80 R - C, -C-alkyl; phenyl R, is the group -N, where R, is water. genus, C-C5 alkyl, phenyl (C, -C4) alkyl; R4 is hydrogen, C, -Cg-alkyl, .group CORj, where RJ is Cd-Cg-alkyl, phenyl, Cz-C, -cycloalkh1, a 5-6-membered unsaturated azbt- or sulfur-containing heterocycle, or R and R together with the common nitrogen atom form a group

"

V Y and Y, m - 1; - ABOUT; A, Z are all meanings;

06.10.80 R is hydrogen, C-Cg-an-alkyl, phenyl, C-Cd-cycloalkyl, R, -C-Cg-alkyl, C, -C (-a-L-coxy, C | -C-alkylamino, hydroxyl, heterocyclic group unsubstituted sludge substituted; X - carbyl; m 1; G - 1; A, Z ,, Z, Y, cheni.

and Yg - all know

The invention relates to a method. obtaining new tetrazole derivatives with valuable therapeutic properties in the stomach and duodenal ulcer and which can be used in medicine.

The known reaction of alkylation of thiols with alkyl halides with the formation of tis esters, which is carried out with heating before and in the presence of hydrogen halide acceptor l3.

The purpose of the invention is a method for producing new tetrazole derivatives having valuable pharmacologetic properties.

The goal is to achieve a tetrazole derivative of the general formula based on the known elimination

ten

YG-N (X), p-K1

3

where R is hydrogen. C, -Cj-alkyl, phenyl or C} -Cd-1D1 -cloalkyl;

X is a carbonyl group or a group —S (0) p;

f and p O or 1 or 2;

ha - O or 1;

A - C, Cp - alkyls;

R - C, -C-alkyl, C-Cd-cycloalkyl. naphthyl, a group of the formula -C (NH) NHR, (where is C, -C-alkyl), phenylalkyl in which alkyl has 1-6 carbon atoms and in which phenyl core can be replaced by halogen, phenyl containing 1- 3 halogen substituents. C, -Cg-alkyl, C-C-alkoxyl, C-C-Alg-konoylamino groups; C-C-alkyl, a substituted heterocyclic group which can have 3 1 substituents selected from C-C-alkyl or amino groups, where the heterocyclic group is selected from pyridyl, furyl thiazolyl, a heterocyclic group with 1-4 hetero atoms from nitrogen, oxygen or sulfur, which may have 1-2 substituents from among alkyl, halogen, carboxyl, oxo group, amino group. C, -C-alkoxycarbonyl, hydroxyl, amino, nitro, phenyl, C., - Cd-cycloalkyl or C -Cg-alkylamino groups, and in the case when m O, R, may also be a group of the formula where R is hydrogen, C (-C-alkyl or phenyl (C, -C5) alkyl; R is hydrogen, C, -Cg-alkyl, group -CZNHR, where Z is sulfur or amino group which may be substituted with C, -C-al Kilohm; Ry-C, -Cg-alkyl or amino, or R4 tetrazolyl, which may be substituted with C, -C5-alkyl or -N-CO-Rg, where RJ is C, -Cj-alkyl , phenyl, which may have 1-3 substituents from among C, -Cg-alkoxy,.-cycloalkyl, or P. - 5- or 6-member saturation geterrtsikl nitrogen or sulfur, or R and R together with the common nitrogen atom, form a group Q

provided that when I is 1 or 2, then m is 1 and X is sulfur or their pharmacologically acceptable acid additive salts.

21 2324

 The method consists in that the hetrazole of the general formula

N

II

NX

-N

 /.

at

where R has the indicated meanings;

Z, is a group U ((where Y is a halogen, mercapto or amidino group), or Z is a group -S (0) -A-Y, in which A, t and Y have the indicated values,

is reacted with a compound of the formula where Y is a mercapto or amidino group in the case when YJ is halogen and Zj is -A- (X) -R (where A, X, m and R have the indicated meanings), and when Z 4 - Y, or Zj, is a group R ,, then Z is a group -S (0) gAY, in the presence of an acceptor of hydrogen halide at a temperature of from room temperature to 200 ° C for 30 minutes to 6 hours, followed by allocation of the target product in the form of a base or acid addition salt.

The process is usually carried out in a solvent, preferably at the boil.

The compounds of general formula I can be converted to pharmaceutically acceptable salts by reacting with a suitable acid. Pharmaceutically acceptable acids include inorganic acids, such as sulfuric, nitric hydrochloride or hydrobromic acid, and organic acids, such as acetic acid, p-toluenesulfonic, ethane sulfonic, oxalic, maleic succinic or benzoic

The compounds obtained according to this method can be easily isolated from the reaction mixture and prepared according to known methods. The separation can be carried out, for example, by distillation, recrystallization, chromatographic separation on a column, extraction, etc.

The compounds of the general formula I or artifactically acceptable coagulums obtained according to the invention have a good inhibitory activity against ulcers formed

with increased nervous load, and ulcers caused by indomethacin, and have fewer side effects, for example, on the central

the nervous system in relation to anticholinergic activity and the degree of gastric digestion; These compounds are valuable medicinal preparations for treating stomach and duodenal ulcers.

Example (reference) .4.6 g of 1-methyl-5-mer-ai to-1, 2,3,4-hetrazole, 9.4 1-bromo-3-chloropropane is dissolved in 100 ml of acetone. To the resulting solution, 6.8 g of potassium carbonate was added and the reaction mixture was boiled under reflux for 3 hours. Acetone was distilled off and water was added to the residue. The reaction mixture is extracted with chloroform, the extract is washed with a saturated aqueous solution of chloride and dried with magnesium sulfate. Chloroform is distilled off and the residue is purified on a chromatographic column filled with silica gel. The substance was eluted with a mixture of benzene and ether (5:: 1 by volume), and 8.5 g of 1-methyl-5- (3-chloropropyl) thio-1,2,3,4-tetrazole were obtained in the form of a colorless animal. , p - 1.5396,

Example 2 {reference). According to example 1, receive:

1-cyclohexyl-5- (3-chloropropyl) thio- -1,2,3,4-tetrazole, colorless liquid, Pd 1.5387;

1-methyl-5- (bromobutyl) thio-1,2,3,4-tetrazole, colorless liquid, n | 1.5530.

Example 3 (reference), 5.6 g of 2-mercaptopyridine and 11.7 g of 1-bromo-3-chloropropane are dissolved in 100 ml of acetone and 6.9 g of potassium carbonate is added to the resulting solution. The reaction mixture is boiled to reverse reflux for 5 hours. Then, acetone is distilled off, water is added to the residue and the reaction mixture is extracted with chloroform. The solution in chloroform is washed with an all-saturated aqueous solution of sodium chloride and dried with magnesium sulfate, chloroform is distilled off, the residue is subjected to purification on a Kieselgel-60 filled chromatograph, the substance is eluted with a mixture of chloroform and methanol, then the eluent is distilled off 8.2 g of 2- (3-chloropropyl) thiopyridine are obtained in the form of a reddish oil.

NMR (90 MHz, CDC1,): 5 2.00-2.40 (2H.multiplet); 3.30 (2H, triplet.

J - 6 Hz); 3.70 (2H, triplet, J “6 Hz); 6.80-7.60 (GZ, multiplet); 8.30-8.50 (1H, multiplet).

Example 4 (reference). According to example 3 receive:

5-amino-2- (3-chloropropyl) thio-1,2-, 3,4-thiadiazole, light yellow needles, t, Sh1. 121-121, (ethanol-water);

5-methyl-2- (4-bromobutsh1) thio-1,3,4-oxadiazole, brown liquid, NMR (90 MHz, CDCl,); , 70-2.30 (4H, multiplet); 2.43 (SA, singlet); 3.17 (2H ,.triplet, J = 6 Hz); 3.43 (2H, triplet, J 6 Hz); 6.79 (1H, doublet, J 4.5 Hz); 8.32 (IH, doublet, J 4.5 Hz).

Example 5 (reference). 1- -Methyl-5- (4-bromobutyl) thio-1,2,3,4-tetrazole, prepared as described in Example 2, is dissolved in 50 ml of formic acid, To the resulting solution was added 2.3 g of 30% - hydrogen peroxide under stirring at room temperature, after which the reaction mixture is left at room temperature for 2 days. The reaction mixture is then diluted with water and extracted with chloroform. The chloroform solution is washed with water, with an aqueous saturated sodium bicarbonate solution and with a saturated aqueous solution of sodium chloride, and then dried with magnesium sulfate. Chloroform was distilled to give 5.5 g of 1-methyl-1,2,3,4-tetrazol-5-yl-4-bromobutyl sulfoxide as a colorless liquid.

NMR (90 MHz, SOSTS), 8: 1.80-2.80 (4H, multiplet); 3.30-3.70 (4H, multiplet); 4.34 (SA, singlet).

Example 6 (reference). 1-Methyl-5- (4-bromobutyl) thio-1,2,3,4-tetrazole, prepared as described in Example 2, is dissolved in formic acid (50 ml). To the resulting solution was added 6.9 g of 30% aqueous solution of hydrogen peroxide, after which the reaction mixture was stirred for 6 hours. Under ice-cooling, sodium sulfate is added to the reaction mixture to decompose excess formic acid. Water was then added to the reaction mixture and the mixture was extracted with chloroform. The chloroform solution is washed with water and a saturated aqueous solution of bicarbonate.

then dried with magnesium sulfate. Chloroform was distilled off and the residue was recrystallized from ethanol to obtain 2.9 g of 1-methyl-I, 2,3,4-tetrazol-5-yl-4-bromobutyl sulfone as colorless flakes with a mp. 83.5-85.5 C.

Example 7 (reference). 2- (3--Chloropropyl) thiopyridine (4.4 g) obtained according to example 3 is dissolved in 40 ml of formic acid. To the resulting solution was added 2.7 g of a 30% aqueous solution of hydrogen peroxide and the reaction mixture was stirred for 3 h at room temperature. The mixture was left at room temperature overnight, diluted with water and extracted with chloroform. The chloroform solution is washed with an aqueous, saturated sodium bicarbonate aqueous solution and with a saturated aqueous solution of sodium chloride, and then dried with magnesium sulfate. Chloroform is distilled off and the residue is purified on a chromatographic column (Kieselgel-60). The substance was eluted with a mixture of chloroform and methanol (50: 1) to give 2-pyridyl-3-chloropropyl sulfoxide (2.7 g) as a colorless liquid.

NMR (90 MHz, ASCS), 8: 1.80-2.60 (2H, multiplet); 2.80-3.50 (2H, multiplet); 3.60 (2H, triplet, J 6 Hz); 7.30-7.50 (1H, multiplet); 7.80-8.10 (2H, multiplet); 8.50 - 8.70 (IH, multiplet).

Example 8 (reference). 3.7 g of 2- (3-chloropropyl) thiopyridine, prepared according to Example 3, is dissolved

in 30 ml of formic acid. To the resulting solution, 6.9 g of a 30% aqueous solution of hydrogen peroxide was added and the reaction mixture was stirred at room temperature for 4 hours. After dilution with water, acidic sodium sulfite was added to the reaction mixture with ice cooling to decompose excess formic acid. The reaction mixture is extracted with chloroform and the extract is washed with water, a saturated aqueous solution of sodium bicarbonate and an aqueous solution of sodium chloride, and then dried with sodium sulfate. Chloroform is distilled off and the residue is purified on a chromatographic column (Kieselgel-60). Elution is carried out with a mixture of chloroform and methanol (50: 1);

to

15

20 123248

4 g of 2-pyridyl-3-chloropropyl sulfone as a colorless liquid.

NMR (90 MHz, CDCl1), S: 2.10-2.50 (2H, multiplet); 3.40-4.70 (4H, multiplet); 7.50-7.70 (1H, multiplet); 7.80-8.20 (2H, multiplet); 8.70-8.80 (W, multiplet).

Example 9 (reference). Sog. For example 8, they get

1-methyl-5- (2-chloroethyl) thio-1,2,3,4-tetrazole, colorless prism crystals (ether), m.p. 48-49.5 ° C;

5-methyl-2- (3-chloropropyl) thio- -1,3,4-oxadiazole, colorless liquid, n 1.5147;

5-methyl-2- (3-chloropropyl) sulfonyl- -1,3,4-oxadiazbl, colorless liquid

bone, front 1.5279.

Example 10 (reference). 20 g (0.15 ml) of acetonitrile was dissolved in carbon disulfide (110 ml) and 37 g (0.27 mol) of 4-chloromethyl acid chloride was added to the resulting solution. Then, 60 g (0.45 mol) of aluminum chloride are slowly added to the reaction mixture with stirring at room temperature. The resulting reaction mixture is boiled under reflux.

30 minutes during 30 minutes and left at room temperature for 2.5 hours. The carbon disulfide is decanted and the residue is drunk in a mixture of ice and concentrated hydrochloric acid.

35 (20 ml). The crystals precipitated in this way are separated by filtration and washed with water. The crystals are slurried in ethanol, and after stirring, the crystals are filtered off.

4Q prom) is added to them with water and recrystallized from ethanol to obtain JO g of y-chloro-4-ycetamido-butyrophenone as colorless granules (ethanol), mp. 157-163 s,

45 Example 11 / reference), 16 g (0.12 mol) of aluminum chloride are suspended in 80 ml of carbon tetrachloride and added dropwise to the resulting suspension while cooling

50 with ice. After the introduction of the reagents was completed, the mixture was stirred for 15 minutes and 7.8 g (0.1 mol) of benzene was added dropwise while the reaction mixture was cooled with ice. After re-stirring while cooling with ice for 1 h, the reaction mixture was poured into a mixture of ice and hydrochloric acid and extracted with carbon tetrachloride. The extract of npohjbiBaioT with water, a saturated aqueous solution of sodium chloride and then dried with anhydrous magnesium sulfate. The dried solution was distilled to give 7.3 g of 5-chloropentyl phenes ketone with mp. 143-150 s / 0.5 mm Hg

Example 12 (reference). 26.7 g of aluminum chloride are introduced into 20 MP of nitrobenzene and added to the obtained dropwise with cooling with ice 15.5 g of 4-chloroacid chloride. While cooling with ice, 12.8 g of naphthalene is slowly added to the obtained reaction mixture and stirring is continued at the same temperature for 30 minutes. After stirring at room temperature for an additional 2 hours, the reaction mixture was drunk into a mixture of ice and hydrochloric acid and extracted with chloroform. The extract in chloroform is washed with water, a saturated aqueous solution of sodium bicarbonate, water and an all-saturated aqueous solution of sodium chloride, and then dried with anhydrous sodium sulfate. The dried solution is distilled, the fraction with m.p. 187-191 G / 1.6 mmHg section bt and purified using chromatography on a column filled with silica gel. The resulting product is crystallized from hexane and then recrystallized from a mixture of hexa and petroleum ether, to obtain 4.2 g of 2-4-chlorobutyryl naphthalene in the form of colorless flakes, so pl. 43-44 C.

Example 13 (reference. 16 g of Go, 12 mol of aluminum chloride is suspended in 80 ml of carbon tetrachloride. To the resulting suspension is added dropwise -18; 6 g (0.12: mol of 4-chloro valeric acid chloride) while cooling the reaction mixture with ice. The mixture is stirred for 15 minutes and 7.8 g (0.1 mol) of benzene is added dropwise to it at a temperature not exceeding 5 ° C. The mixture is then kept at the same temperature for another 1 hour, after which the reaction mixture the mixture is poured into a mixture of ice with hydrochloric acid and extracted with chloroform. The extract is washed with water with a saturated aqueous solution of sodium bicarbonate, water, and a saturated aqueous solution of sodium chloride, and then dried with anhydrous magnesium sulfate. Chloroform is evaporated

s

10 15 20 25

50

212324.

and the resulting crystals are recrystallized from hexane, 8.3 g of 4-chlorobutylphenyl ketone are obtained as

Of

35

40

colorless flakes, so pl. 49-50 C.

Example 14 (reference). The following compounds are prepared according to the method indicated in the examples:

Y is chloro-3,4-dimethoxybutyrphenone, light yellow crystals in the form of prisms (ligroin) so pl. 90-92 s;

2- (y-hLorbutiryl) furan, NMR o (SOSTS): s2.0-2.5 (2H, multiplet); 3.00 (2H, triplet, J = 7 Hz); 3.62 (2H, triplet, J 6 Hz); 6.47 (1H, multiplet); 7.14 (1H, doublet, J 4 Hz); 7.51 (W, doublet, J 2 Hz);

y-chloro-4-ethylbutyrophenone, colorless liquid, bp. D41-148 s7 / 0.9 mm Hg;

y-chloro-4-methoxybutyrophenone, colorless flakes (petroleum ether, ethyl acetate), so pl.

2- (y-chlorbutyrnl) pyrrole, NMR (C1) SC, 5: 2.0-2.5 (2H, multiplet); 2.96 (2H, triplet, J = 7 Hz); 3.63 (2H, triplet, J = 7 Hz); 6.25 (1H, multiplet); 6.85-7.18 (2H, multiplet); 10.2 (1H, broad signal, 1H);

2- (y-chlorbutyrsh1) -5-methylthiophene, NMR (CDC1,), 8: 2.0-2.5 (2H, multiplet); 2.52 (ZN, singlet; W, 04 (2H, triplet, J 7 Hz); 3.62 (2H, triplet, J 6 Hz); 6.74 (1H, doublet, J 4 Hz); 7.48 (1H, doublet, j 4 Hz);

3- (U-chlorobutyryl) -2,5-dimethylfuran, 5ShR (AHSC) 8: 2.0-2.5 (2H, multiplet); 2.27 (SA, singlet); 2.54 (SA, singlet); 2.84 (2H, triplet, J = 7 Hz); 3.16 (1H, singlet 3.60 (2H, triplet, J 6 Hz);

2- (y-chlorbutyrsh1) -5-chlorothiophene, colorless liquid, 139-144 C / / 0.75 mm Hg;

2- (} -chlorobutyryl pyridine, colorless liquid, NMR (HSCC), 8. 2.23 (2H, multiplet); 3.43 (2H, triplet, J 7 Hz); 3.68 (2H, triplet J 7 Hz ); 7.2-8.1 (3N, multiplet); 8.63 (1H, doublet).

Example 15 (reference). From 1.9 mg, 11.2 g and 80 ml of dry

55 ether is prepared by Grignard reagent, to which is added dropwise with ice-cooling a solution of 7 g of 4-chlorobutyronitrile in 15 ml of ether, peretilenketketal Z-bromopropylcyclohexyl ketone, NMR (CDCl,), 8 and 0.9-2. , 2 (15H, multiplet); 3, 40 (2H, triplet, J 6 Hz); 3.93 (4H, syn- 5g);

3-chloropropyl- |} -phenylethylketone, so pl. .130-139 s / 0.25 mm Hg

2- (4-chlorobutyryl) -5-methoxycarbonylfuran, CDCl, 8. 2.0-2.5 (2H,

sew the reaction mixture at the same temperature for 2 hours and at room temperature for another 2 hours. Then 10% hydrochloric acid is slowly added dropwise to the reaction mixture while cooling the mixture with ice to pH 1. After stirring the reaction the mixture for I h at room temperature, it is extracted with ether. The ether layer is washed - 10 multiplets); 3.11 (2H, triplet, filled with a saturated aqueous solution of bicar-J 7 Hz); 3.63 (2H, triplet, J sodium bonate, and a saturated aqueous 6 Hz); 3.93 (SA, singlet); sodium chloride solution, after chet 7.1-7.3 (2H);

It is dried with magnesium sulfate. The solution of (6- (4-chlorobutyryl) -3,4-dihydrocarbon) is distilled off and the residue is subjected to 15 bostyryl, light yellow needles. distillation, obtain 1.6 g of 3-chloropropyl-crystals (acetone.), mp, 158-160 C. of butyl ketone, bp. 104-10b / Example 1. 1-MetSH1-5-mer / 30 mm Hg Capto-1,2,3,4-tetrazole (1.2 g)

dissolved in acetone (50 ml). 3-bromopropylphenylgly sulfide (2.5 g) and potassium carbonate (1.5 g) are added to the solution, the mixture is heated under reflux for 4 hours. The acetone is distilled off and water is added to the residue.

3-chloropropyl benzyl ketone, colorless - 25 The mixture is extracted with chloroform ,. Chlorine liquid, bp 108-119 with / roformny solution washed with saturated / 0.15 mm Hg aqueous sodium chloride and dried

magnesium sulfate. Chloroform was distilled off and the residue was purified by chromatographic p. And meper 16 (reference). The following compounds are prepared according to the indicated method:

3-chloropropylcyclopentyl ketone, colorless liquid, bp 127-137 ° C / 22 mmHg;

3-bromopropylcyclohexyl ketone, NMR (CDCe,), 5: 1.2-2.4 (PN, multiplet) - 2.0-2.5 (2H, multiplet); 2.64 (2H, 30 graphs on the column (Kieselgel-60) triplet, J = 7 Hz); 3.44 (2H, triplet using J 6 Hz as eluent) .. benzene-chloroform mixture (3: 2), get I-methyl-5- (3-phenylthiopropsh1) thio -1,2,3,4- tetrazole (1.8 g) in the form of

Example 17 (reference).

1.5 g of 3-chloropropyl ketone solution of a colorless liquid, n 1.6006.

10 MP of ethylene glycol and to semi-

Calculated,%: C 49.60; H 5.30; N 21.03

C, H, 4N, Si

2 g of ortho-formate and 0.2 g of p-toluenesulfonic acid are added to the solution. The reaction mixture is stirred at room temperature for 5 hours. After neutralization with sodium hydroxide, water is added to the reaction mixture and the mixture is extracted with ether. The ether solution is washed; water and a saturated aqueous solution of sodium chloride, then dried with magnesium sulfate. The ether is distilled off and the residue is dispersed under reduced pressure, to obtain 1.3 g of ethylene ketal 3-chloropropylethyl ketone, b.p. 98-102 / 33 mm Hg.

Example 18 (reference). According to Example 17, the following compounds are prepared:

4-chlorobutyrophenone ethylene ketal, 5tP (AHSC), 8: 1.8-2.2 (4H, multipet); 3.43 (2H, .m triplet, J 6 Hz); 3.65-4.0 (4H, multiplet); 7.1-7.5 (5H, multiplet)

40

Found,%: C 49.70; H 5.13;

N 20.94.

45

50

Example 2. According to example 1, receive:

1-methyl-5- (3-cyclohexylthiopropyl) thio-1,2,3,4-tetrazole, colorless liquid, HD 1.5433;

1-phenyl-5- 4- (1-phenyl-1,2,3,4-g-tetrazol-5-yl) thiobutyl D thio-1,2,3,4-tetrazol, colorless needles (ethanol-chloroform) mp: 127-128.5 ° C;

1-methyl-5- 3- (1-cyclohexccc1-. -1,2,3,4-tetrazol-5-yl) thiopropylTio- -1,2,3,4-tetrazole, pale yellow, liquid, front 1,5653; 1-phenyl-5-z- (1-phenyl-1,2,3,4g-tetrazol-5-yl) thiopropyl thio-1,2,3,4-tetrazole, colorless needles (methanol-chloroform), t , pl, 81-82 ° C;

ethylene ketal Z-bromopropylcyclohexyl ketone, NMR (CDCl,), 8 i 0.9 - 2.2 (15H, multiplet); 3, 40 (2H, triplet, J 6 Hz); 3.93 (4H, singlet);

3-chloropropyl- |} -phenylethylketone, so pl. .130-139 s / 0.25 mm Hg

2- (4-chlorobutyryl) -5-methoxycarbonylfuran, CDCl, 8. 2.0-2.5 (2H,

multiplet); 3.11 (2H, triplet, J = 7 Hz); 3.63 (2H, triplet, J 6 Hz); 3.93 (SA, singlet); 7.1-7.3 (2H);

40

Found,%: C 49.70; H 5.13;

N 20.94.

Example 2. According to example 1, receive:

1-methyl-5- (3-cyclohexylthiopropyl) thio-1,2,3,4-tetrazole, colorless liquid, HD 1.5433;

1-phenyl-5- 4- (1-phenyl-1,2,3,4-g-tetrazol-5-yl) thiobutyl D thio-1,2,3,4-tetrazol, colorless needles (ethanol-chloroform) mp: 127-128.5 ° C;

1-methyl-5- 3- (1-cyclo-hex-1-. -1,2,3,4-tetrazol-5-yl) thiopropyl T-1,2,3,4-tetrazole, pale yellow liquid , Front 1.5653; 1-phenyl-5-z- (1-phenyl-1,2,3,4g-tetrazol-5-yl) thiopropyl thio-1,2,3,4-tetrazole, colorless needles (methanol-chloroform), t , pl, 81-82 ° C;

1 -methyl-5 O (1-methylimidazole 2- - l) thiopropyl thio-I, 2,3,4-tetrazole, colorless needles (ether,

m.p. 59.5-BS, 5 C; 1-methyl-5- 3- (2-pyridyl) thiopropyl 1 5 thio-1, 4-tetrazole, pale yellow liquid, ni, l, 6022j

t-methyl-5- 2- (1-methyl-1,2,3,4-tetrazol-5-nl) thioethyl thio-1,2,3,4-tetrazole, colorless prisms (ethanol-chloroform ), mp, 145-147 C;

1-methyl-5- | 3-metsh-3- (5-methyl--1,3,4-oxadiazole-2-cl) thiopropyl, thio--1,2,3,4-tetrazole, colorless liquid

to

Found,%: C 42.43; H 4.30} N 27.53.

Example 4. According to example 3, the following compounds were prepared;

1-methyl-5 4- (2-pyridyl) thiobutyl thio-1,2,3,4-tetrazole, pale yellow prisms, mp. 49-51.5 ° C (ethanol-water); 1-methyl-5-p- (2-pyridyl) thiopentyl3 thio-i 2,3.4-tetra-el, colorless oil, Pd 1.5853;

-methyl-5-1b- (2-pyridyl) thiohexen1 thio-1,2,3,4-tetrazole, colorless

prisms m.p. 58-69 ° C (ethanol); 151-methyl-5-з- (3-hydroxy-2-pyridsh1)

1-methyl-5- (1-methyl-1,2,3,4-tetrathiopropyl thio-1,2,3,4-tetrazole, bled-) thiomers1 thio-1,2,3,4-tetra- but yellow granules, so pl. 87.5-88.5 С

ashes, colorless flakes (methanol - (hexane - type-acetate);

chloroform), so pl. .i56-i59 ° C; 1-methyl-5- 3- (4-methyl-2-pyrimidyl)

1-methyl-5-Hz- (5-methyl-1,2,4-oxag thiopropyl thio-1,2,3.4-tetrazole, colorless liquid, 1.5853 ;.

1-methyl-2- 4- (1-methyl-1, 2,3,4-tetrazol-5-yl) thiobutyl isothiourea hydrobromide, white powder (aceton-25 tone), T.Sh1. 116.5gP8.5 with (with,);

1-metil-5-G 3- (2-benzimidazolyl) tIo-propyl thio-1,2,3,4-tetrazral, colorless needles ethanol), m.p. 137-139 ° C; J -metsh1-5-z- (3,5-di-tert. Butyl, 1,5553;

diazol-2-yl) sulfonylpropyl thio- -1,2,3,4-tetrazole, pale yellow liquid, 1.5598;

1-Cyclohex®1-5- (3-ethylthiopropyl) thio-1,2,3,4-tetrazole. colorless liquid, Hjj "1.5433;

1-methyl-5-z- (1-methylt1,2,3,4-β-tetrazol-5-yl) thiopropyl thio-1,2,3,4. 11. (-methyl-d-1 -CH, - di-tert.uyl-

-tetrazol, colorless prisms (ethanol). . h t loo /

,.,., :: about „30-4-hydroxyphenyl) thiopropyl thio-1,2,3,4t. pl. IHI.J-lAj.b Ll “J y

m.p. 141.5-143,

1-metsh1-5-4- (1-methyl-1,2,3,4-β-tetrazol-5-yl) thiobutsh thio-1,2,3,4-tetrazole, colorless needles (ethanol), t. square 122-123 ° C

Example 3. 1-Metip-5-mercapto-1,2,3,4-tetrazole (1.2 g); dissolved in acetone (50 ml). To the solution is added 2- (2-chloroethyl) thi-pyrvdine (2.0 g and potassium carbonate (1.5 g, the mixture is refluxed for 4 hours). Ace + it is distilled off and water is added to the residue. The mixture is extracted with chloroform. The chloroform solution is washed with saturated aqueous sodium chloride and dried with magnesium sulfate. The chloroform is distilled off and the residue is purified by chromatography on a silica gel (Kiesel gel-60). The column is eluted with chloroform-methanol and the product is recrystallized from ethanol, made -methyl-5- 2- - (2-pyridsh1) TIOETSH1 typ-1,2,3,4-tetrazole (1.5 g) as a colorless tny prisms, mp 77-79,5 ° C.

Calculated,%; C 42.67; H 4.38; N 27.64

C, H ,, N, Sj

tetrazole, pale yellow needles (methanol-water), so pl. 76-77 C;

1-methyl-5-z- (5-amino-, 3,4-thiadiazol-2-yl) thiopropyl} thio-1, 2,3,4-tetrazol, colorless prisms (ethanol) so pl. 120.5-122 ° C; ; 1-methyl-5-z- (5-methyl-.1,2,4-oxydiaeol-2-yl) thiopropyl thiot1,2,3,4-tetrazol, colorless liquid,

. 1.5644;

40) -methyl-5- 3- (p-naphthyl) thiopropyl

thio-1,2,3,4-tetrazole, colorless needles (ethanol), so pl. 56-58 C;

1-methyl-5- 3- (2-quinolyl) thiopropyl thio-1,2,3,4-tetrazole, pale yellow needles (methanol), so pl. 87-89 C;

1-metsh1-5- (4-phenylthiobutyl) thio- -1,2,3,4-tetrazole, colorless needles (ethanol), so pl. 51.5-53 ° .С:

1-methyl-5-4 .- (2-carbroxyphenyl) thiobutyl Dthio-1,2,3,4-tetrazole, pale yellow prisms (ethanol), mp. 143, 5-144,5 С;

1-methyl-5-L4- (2-methylfensh1) thiobutythyl thio-1,2,3,4-tetrazole, colorless liquid, n 1.5786;

f-methyl-5-4- (2-aminofensh1) thiobutyl thio-1,2,3,4-tetrazole, yellow liquid, p 1.5961;

to

 "J y

tetrazole, pale yellow needles (methanol-water), so pl. 76-77 C;

1-methyl-5-z- (5-amino-, 3,4-thiadiazol-2-yl) thiopropyl} thio-1, 2,3,4-tetrazol, colorless prisms (ethanol) so pl. 120.5-122 ° C; 1-methyl-5-z- (5-methyl-.1,2,4-oxydiaeol-2-yl) thiopropyl thiot1,2,3,4-tetrazol, colorless liquid,

. 1.5644;

0) -methyl-5- 3- (p-naphthyl) thiopropyl

thio-1,2,3,4-tetrazole, colorless needles (ethanol), so pl. 56-58 C;

1-methyl-5- 3- (2-quinolyl) thiopropyl thio-1,2,3,4-tetrazole, pale yellow needles (methanol), so pl. 87-89 C;

1-metsh1-5- (4-phenylthiobutyl) thio- -1,2,3,4-tetrazole, colorless needles (ethanol), so pl. 51.5-53 ° .С:

1-methyl-5-4 .- (2-carbroxyphenyl) thiobutyl Dthio-1,2,3,4-tetrazole, pale yellow prisms (ethanol), mp. 143, 5-144,5 С;

1-methyl-5-L4- (2-methylfensh1) thiobutythyl thio-1,2,3,4-tetrazole, 5 colorless liquid, n 1.5786;

f-methyl-5-4- (2-aminofensh1) thiobutyl thio-1,2,3,4-tetrazole, yellow liquid, p 1.5961;

1-methyl-5- 4- (4-chlorophenyl) thiobutyl thio-1,2,3,4-tetrazole, colorless liquid, nj, 1.5971;

I-methyl-5-3- (2-furylmethyl) thiopropyl thio-1,2,3,4-tetrazole, brown liquid, Pd 1.5641;

1-methyl-5- (3-benzylthiopropyl) thio-I, 2,3,4-tetrazole, colorless liquid, 1.5856;

1-methyl-5- 3- (4-chloro-benzyl) thio-propyl thio-, 2,3,4-tetrazole, colorless liquid, nJ, 1.8585;

1-methyl-5-Gz- (4,5-dimethyl-1,2,4-triazol-3-sh1) thiopropyl thio-1,2,3,4-tetrazol, colorless prisms (ethanol, hexane), t .pl. 74-77 C;

1-methyl-5- (3-quinazolin-4-one-2- -Sh1) thio-1,2,3,4-tetrazole, colorless flakes (ethanol-hexane), m.p. 132.5 134.5 C;

1-methyl-5- 4- (3N, 4H-1,3,4-benzo-Triazepin-5-one-2-yl) thiobutyl thio- -1,2,3,4-tetrazole, colorless primer, t .pl. 94-95 ° C (methanol);

1-methyl-5- (3-ethlthiopropyl) thio- - 1, 2, 3,4-tetrazole, colorless liquid, Pr 1,5385;

1-methyl-5- (3n-butylthiopropyl) thio -1,2,3,4-tetrazole, yellow liquid, 1.5192;

1-methyl-5- (3-cycloheptylthiopropyl thio-1,2,3,4-tetrazole, pale yellow liquid, n 1.5469;

1-methyl-5- 3- (2-pyridylmethyl) thiopropyl thio-1,2,3,4-tetrazole, brown liquid, p 1.5820;

1-methyl-5-3- (4-methyl-2-thiazolyl thiopropyl thio-1,2,3,4-tetrazole, colorless liquid, Pr 1.5919;

I-methyl-5-Z- (4-pyridyl) thiopropyl thio-1,2,3,4-tetrazole, pale yellow liquid, Pr 1.6017;

1-methyl-5- З- (5-nitro-2-pyridyl) thiopropyl thio-1., 2,3,4-tetrazole, pale brown liquid, n 1,6289

1-methyl-5-Z- (2-amino-4-metsh1-6-pyrmidinyl thiopropyl thio-1,2,3,4-tetrazole, colorless powder (methanol), mp 119-120 ° C;

1-metshg-5- 2- (2-furylmethyl) thioethyl thio-1,2,3,4-tetrazole, pale brown liquid, p 1.5711;

1-methyl-5-З- (2-amino-4-thiazolyl) metsh1 thiopropyl thio-1, 2,3,4-tetrazol, yellow prisms (methanol-water, mp 117-118,

1-cyclohexgsh-5- 3- (1-cyclohexyl-I, 2,3,4-tetrazol-5-yl) thiopropyl

p5

thio-1,2,3,4-tetrazole, pale yellow granules (ether-ethanol), so pl. 88.5-89.5 C;

1-methyl-5-Z- (1-phenyl-1,2,3,4-β-tetrazol-5-yl) thiopropyl-Thio-1,2,3,4-tetrazole, colorless prisms (ethanol ligroin), t .pl. 89-90.5 ° C;

1-methyl-5- 5- (1-metsh1-1,2,3,4-β-tetrazol-5-yl) thiopentyl thio-1,2,3,4-β-tetrazole, colorless prisms (ethanol) t.pl . 64-65 ° C;

1-methyl-5-b- (1-methyl-1,2,3,4-β-tetrazol-5-yl | thiohexyl thio-1,2,3,4-tetrazole, colorless prisms (acetone) 5 t. square 91-93.

1-methyl-5- 2-metsh1-3- (1-methyl7 -1,2,3,4-tetrazol-5-yl) thiopropylthio

-I, 2,3,4-tetrazole, colorless prisms (ethanol), so pl. 87-89.5 C;

0 1-methyl-5- 3-MeTHjr 3- (i-methyl-1, 2,3,4-tetrazol-5-yl) THonponmrJ

thio-1,2,3,4-tetrazole, colorless

needles (ethanol), so pl. 68.5-70.5 C;

1-methyl-5- | 2-methyl-3- (2-pyridyl)

5 thiopropyl thio-1,2,3,4-tetrazole, pale yellow liquid, Hjj 1.5936;

1-methyl-5- 4- (4-methoxyphenyl) thiobuty l-thio-1,2,3,4-tetragzol, colorless liquid, NMR (90 MHz, CDClI),.

0: 1: 1.50-2.20 (4H, multiplet); 2.83 (2H, triplet, J 6 Hz); 3.30 (2H, triplet, J 6 Hz); 3.77 (SA, singlet); 3.87 (SA, singlet); 6.82 (2H, doublet, J 9 Hz); 7.32 (2H,

5 doublet, J 9 Hz).

Example 5. 1-Methyl-5-mercapto-1,2,3,4-tetra sol (1.2 g) is dissolved in acetone (50 ml). 1-methyl-5- (3-chloro-octyl) thio-1,2,3,4-tetrazole (4.1 g) and potassium carbonate (1.5 g) are added to the solution and the mixture is heated under reflux to for 4 hours. Aldeton is distilled off and water is added to the residue. The mixture is extracted with chloroform. The chloroform solution is washed with saturated aqueous sodium chloride and dried over magnesium sulfate. Chloroform is distilled off with chgg, and the residue is recrystallized from a mixture of ethyl acetate and hexane to give 1-methyl-5-8- (l-methyl -1,2,3,4-tetrazol-5-yl) thioocto thio-1, 2,3,4-tetrazole (2.0 g) as colorless needles, so pl. 52-54 С,

5 Example 6. In accordance with example 5, receive:

I -methyl-5-3- (3-methoxy-2-pyridyl) typrosh "Jthio-l, 2,3,4-tetrazole,

colorless needles (ethanop) tpl, ZZ.Z-ZZ C;

1-methyl-5- 3- (2-aminothiazo; p-5-yl) methylthiopropyl thio-1,2,3,4 tetrazole, yellow prisms (methanol-water), mp, 117-118.5 ° WITH.

Example 7. 1-Methyl-5-chloro--1,2,3,4-tetrazole (1.18 g) and thiourea (0.8 g) are dissolved in ethanol (50 ml) and the solution is boiled with reflux for 3 hours. After cooling, the precipitated crystals are filtered off and dried. The crystals were dissolved in ethanol (50 ml), 2- (2-chloro-ethylate 1) thiopyridine (1.7 g) and Yu% aqueous sodium hydroxide (5 ml) were added to the solution. The mixture was heated under reflux. 3 hours. Ethanol is distilled off and water is added to the residue. The mixture was extracted with chloroform. The extract was washed with saturated aqueous sodium chloride and dried with magnesium sulfate. Chloroform is distilled off, the residue is purified by column chromatography (Kieselgel-60, eluent {chloroform}. The product is recrystallized from ethanol, lmethyl-5- 2- - (2-pyridyl) thio, 2,3,4 -tet-razol (0.7 g) in the form of colorless prisms, t, mp, 77-79.5 s,

Calculated,%: C 42.67; H 4.38; H 27.64

C, H ,, N, S

35

Found,%: C 42.53; H 4.29; N 27.38,

Example 8, According to example 7, receive:

1-metsh1-5-4- (2-pyridyl) thiobutyl thio-I, 2,3,4-tetrazole, pale yellow 40 prisms, t, Sh1, 49-51, (etadol-water a;)

1-methyl-5-1.5- (2-pyridyl) thiopentsht thio-1,2,3,4-tetrazole, colorless liquid, p 1,5853;

1-methyl-5- {6 (2-pyridyl) thiohex®1 45

thio-1,2,3,4-tetrazole, colorless prisms, t, mp, 58-60 ° C (ethanol);

1-methyl-5-3- {4-methyl-2-pyrimidyl) thiopropyl} thio-G, 2,3,4-tetrazole, colorless liquid, "1.5853; 50

1-methyl-5-3- (2-benzimidazolsh1) tnopropyl thio-1,2,3,4-tetrazole, colorless needles (ethanol)., Mp, 137-

1-methyl-5- 3- (3,5-dk-tert.butyl- 55 -4-hydroxyphenyl) thiopropyl thio-1,2,3 4 -tetrazol, pale yellow needles (methanol water), mp . 76-77 ° C;

0 5 0 5 0

five

0

five

five

1-methyl-5- 3- (5-amino-1,3,4-thiadnazole-2-yl) thiopropyl thio-1,2,3,4-tet raeol, colorless prisms (ethanol), t, b1 , 120.5-122 ° C;

1-methyl-5-3- (5-methyl-1,3,4-ox7-diazol-2-yl) thio-propyl thio-1,2,3,4-tetrazole, colorless liquid, 1.5644;

1-methyl-5- 3- (y-naphthyl) thiopropyl | thio-1,2,3,4-tetrazole, bé: colored needles (ethanol), mp, 56-58 ° C; f 1-methyl-5-p-C2-quinolyl) thioproxy thio-1,2,3,4-tetrazole, pale yellow needles (methanol), mp, 87-89 C;

1-methyl-5- (4-phenylthiobutyl) thio-, 2,3,4-tetrazole, colorless prisms (ethanol), so pl. 51.5-53 ° C;

I-methyl-5-t4- (2-carboxyphenyl) thiobutyl thio-1,2,3,4-tetrazole, pale yellow prisms (ethanol), mp, 143.5-144.5 ° C;

1-methyl-5- 4- (2-methylphenyl) thiobic tio-1,2,3,4-tetrazole, colorless liquid, n | 1.5786;

. 1-me TSH1-5-4- (2-aminophenyl) thio-6yTHnJ thio-1,2,3,4-tetrazole, yellow liquid, ne 1.5961;

ABOUT

1-methyl-5- 4- (4-chlorophenyl) thiobutylP thio-1,2,3,4-tetrazole, colorless liquid, Id 1.5971;

1-methyl-5-W-g (furmetme), thiopropyl thio-1,2,3,4-tetrazole, brown liquid, 1.5641 f

1-methyl-5- (3-benzylthiopropyl) thio- -1,2,3,4-tetrazole, colorless liquid, 1.5X56;

1-methyl-5- 3-4-chlorobenzyl) thi-nponHnJTHb-1, 2,3,4-tetrazole, colorless liquid, P 1,5858;

1-methyl-5-Z- (4,5-dimethyl-1,2,3,4-triazol-3-yl) thioprosh} thio-1,2,3,4-tetrazole, colorless prisms (ethanol -hexane), so pl. 74-77 C;

1-methyl-5-z- (quinazol-4-OH-2-yl) thio-propyl thio-1,2,3,4-tetrazole, colorless flakes (methanol-hexane), m.p. 132-5-134.5 s;

1-methyl-5- 4- (3N, 4H-1,3,4-benzotriazepin-5-one-2-sh1) thiobutyl thio- -1,2,3,4-tetrazole, colorless prisms, t .pl. 94-95 0 (methanol);

1 -wetil-5- (3-ethylthiopropyl) thio- -1,2,3,4-tetrazole, colorless liquid, 1.5385;

I-methyl-5- (3-n-butylthiopropyl) thio-1,2,3,4-tera az ol, yellow and liquid, 1.3192;

nineteen

1-methyl-5- (3 cycloheptylthiropropyl) thio-1,2,3,4-tetrazole, pale yellow yellow, - 1.5469;

1-methyl-5-z- (2-pyridylmethyl) thiopropyl thio-1,2,3,4-tetraeol, brown liquid, p 1.5820;

1-methyl-5-z- (4-methyl-2-thiazolyl) thiopropyl thio-1,2,3,4-tetrazole, colorless liquid, p 1.5919}

1-methyl-5-Z- (4-pyridyl) thiopropyl thio-1,2,3,4-tetrazole, pale yellow

fluid, front

1.6017;

1-methyl-5-z- (5-nitro-2-pyridsh1) thioprothst thio-1,2,3,4-tetrazole, pale brown liquid, “- 1.62289;

1-methyl-5-z- (2-amino-4-methyl-6-pyrimidyl) thiopropyl thio-1,2,3,4-tetrazole, colorless powder (methanol), m.p. 119-120 ° C;

1-meth-1-5- 2- (2-furylmethyl) thioethyl thio-1,2,3,4-tetrazole, pale brown liquid, 1.5711;

1-methyl-5- | 3- (2-amino-4-thiazolyl) methyl thiopropyl thio-1,2,3,4-tetrazole, yellow prisms (methanol-water), so pl. A7-118,5 ° C;

1-cyclohexyl-5- 3- (1-cyclohexyl-1, 2,3,4-tetrazol-5-yl) thiopropyl-thio-1,2,3,4-tetrazole, pale yellow granules ( ether-ethanol), so pl. 88.5-89.5 ° C;

1-methyl-5-z- (1-phenyl-1,2,3,4-β-tetrazol-5-Sh1) thiopropyl-tione liquid, NMR (90 MHz, CDC1) S :. 1.50-2.20 (4H, m); 2,83Ч2Н, T..J «- 6 Hz); 3.30 (2H, t. J 6 Hz); 3.77 (ЗН, s); 3.87 (ЗН, s); 6.82 (2H, d. 5 J 9 Hz); 7.32 (2H, d, J 9 Hz);

I-methyl-5- (3-phenylthiopropyl) thio- -1,2,3,4-tetrazole, colorless liquid, Pd 1.6008;

1-methyl-5- (3-cyclohexyl-1-thiopropyl to thio-1,2,3,4-tetrazole, colorless liquid, P. D 1.5433;

1-methyl-5-з- (2-ПИРИДШ1) thiopropyl thio-1,2,3,4-tetrazole, pale yellow liquid, Pdz 1.6022;

1-cyclohexyl-5- (3-ethylthioproth) thio-1,2,3,4-tetrazole, colorless liquid, Pp 1.5433 ;.

I-methyl-5-z- (I-methyl-1,2,3,4-β-tetrazol-5-yl) thiopropyl thio-1,2,3,4-β-tetrazole, colorless prisms, mp.

15

20

25

thirty

141.5-143,

1-methyl-5- - (1-methyl-, 2,3, razol-5-ip) thiobutyl thio-1,2,3,4-tet razol, colorless needles, mp, 122–123 ° C;

1-phenyl-5- 4- (1-fench1-1,2,3,4-β-tetrazol-5-yl) thiobutyl thio-1,2,3,4-tetrazole, colorless needles (ethanol-chloroform), m.p. 127-128,

1-methyl-5-z- (1-cyclohexyl-1,2, 3,4-tetrazol-5-yl) thiopropyl thio- -1,2,3,4-tetrazole, pale yellow liquid, PD 1.5853 ; . .

1-phenyl-5-з- (1-phenyl-1,2,3,4-.

-1,2,3,4-tetrazole-, colorless prisms 35 tetrazol-5-yl) thioproxy1 thio-1,2,3,4. (Ethanol-ligroin), mp. 89-90,

1-methyl-5-5-1-methyl-1,2,3,4-tetrazol-5-yl) thiopentyl thio-1,2,3,4-tetrazol, colorless prisms (ethanol) so pl. 64-65 ° C;

-methyl-5-b- (1-methyl-1,2,3,4-β-tetrazol-5-yl) thiohexyl thio-1,2,3,4-tetrazole, colorless prisms (acetone) so pl. 91-93.5 ° C;

1-methyl-5- 2-methyl-3- (1-methyl--1,2,3,4-tetrazol-5-yl) thiopropyl thio-1,2,3,4 tetrazole, colorless prisms (ethanol), 87 -89.5 ° C;

1-methyl-5-3-methyl-3- (1-methyl-tetrazole, colorless needles (methanol-chloroform), mp 81-82 ° C;

.1-methyl-2-3- (1-methylimidazol-2-yl-thiopropyl thio-1,2,3,4-tetrazole, 40 colorless needles (ether), mp 39.5-60 ,.

Example 9; 2-111-3-chloropropyl sulfone (2.2 g) and 1-methyl-45 -.5-mercapto-1,2,3,4-tetrazole (1.2) is dissolved in acetone (50 ml ), Potassium carbonate (1.4 g) is added to the solution and the mixture is heated under reflux for 5 hours. Acetone

-I, 2,3,4-tetrazol-5-yl) thiopropyl thio-50 was distilled off and water was added to the residue. -1,2,3,4-tetrazole, colorless needles (ethanol) so pl. 68.5-70.5 ° C;

1-methyl-5-2-methyl-3- (pyridyl) thiopropyl thio-1,2,3,4-tetrazole,

29 5

pale yellow liquid, Pr 1.5936;

1-methyl-5- (4-methoxyphenyl) thio-butyl-thio-1,2,3,4-tetrazol, without a mixture The mixture is extracted with chloroform. The chloroform solution is washed with acetic sodium chloride and dried over magnesium sulfate. Chloroform was distilled off, 55 and the residue was purified by column chromatography (Kieselgel 60). The column is eluted with a mixture of chloroform and methanol and the product of cerealcrystalline21232420

liquid, NMR (90 MHz, CDC1) S :. 1.50-2.20 (4H, m); 2,83Ч2Н, T..J «- 6 Hz); 3.30 (2H, t. J 6 Hz); 3.77 (ЗН, s); 3.87 (ЗН, s); 6.82 (2H, d. 5 J 9 Hz); 7.32 (2H, d, J 9 Hz);

I-methyl-5- (3-phenylthiopropyl) thio- -1,2,3,4-tetrazole, colorless liquid, Pd 1.6008;

1-methyl-5- (3-cyclohexyl-1-thiopropyl to thio-1,2,3,4-tetrazole, colorless liquid, P. D 1.5433;

1-methyl-5-з- (2-ПИРИДШ1) thiopropyl thio-1,2,3,4-tetrazole, pale yellow liquid, Pdz 1.6022;

1-cyclohexyl-5- (3-ethylthioproth) thio-1,2,3,4-tetrazole, colorless liquid, Pp 1.5433 ;.

I-methyl-5-z- (I-methyl-1,2,3,4-β-tetrazol-5-yl) thiopropyl thio-1,2,3,4-β-tetrazole, colorless prisms, mp.

15

20

25

thirty

141.5-143,

1-methyl-5- - (1-methyl-, 2,3, razol-5-ip) thiobutyl thio-1,2,3,4-tet razol, colorless needles, mp, 122–123 ° C;

1-phenyl-5- 4- (1-fench1-1,2,3,4-β-tetrazol-5-yl) thiobutyl thio-1,2,3,4-tetrazole, colorless needles (ethanol-chloroform), m.p. 127-128,

1-methyl-5-z- (1-cyclohexyl-1,2, 3,4-tetrazol-5-yl) thiopropyl thio- -1,2,3,4-tetrazole, pale yellow liquid, PD 1.5853 ; . .

1-phenyl-5-з- (1-phenyl-1,2,3,4-.

35 tetrazol-5-yl) thiopropsh1 thio-1,2,3,4 tetrazol-5-yl) thiopropsh1 thio-1,2,3,4-tetrazole, colorless needles (methanol-chloroform), so pl. 81-82 ° C;

.1-methyl-2-3- (1-methylimidazol-2-yl-thiopropyl thio-1,2,3,4-tetrazole, colorless needles (ether), mp 39.5-60 ,.

Example 9; 2-111-3-chloropropyl sulfone (2.2 g) and 1-methyl-5-mercapto-1,2,3,4-tetrazole (1.2) are dissolved in acetone (50 ml) Potassium carbonate (1.4 g) was added to the solution and the mixture was heated under reflux for 5 hours. Acetone

distilled off and added to the residue. water

The mixture is extracted with chloroform. The chloroform solution is washed with acetic sodium chloride and dried over magnesium sulfate. Chloroform is distilled off, and the residue is purified by column chromatography (Kieselgel 60). The column was eluted with a mixture of chloroform and methanol, and the product was recrystallized from ethanol to give 3- (l-methyl-1, 2,3,4-tetrazole 5-yl) thiopropyl-2-pyridyl sulfone (1 g) as colorless prisms, t .pl. 98.5-.

Calculated,%: C 40.12; H 4.38; M 23.39

CtoH NySjO

Found,%: C 40.02; H 4.46; N 23.29

Example 10. In accordance with example 9 receive

H-C is ethyl-1,2,3,4-tetrazol-5-yl) thiopropyl-2-pyridyl sulfoxide, colorless prisms (ethanol), so pl. 88.5-90,

Analogously to example 9 receive;

1-T4etch1-5g H- (3,4-dihydrocarbo-yl) propylthio -1,2,3,4-tetrazol, colorless liquid, ttj, «- 1.5928;

1-methyl-5-3- (1-methyl-1,2,3,4-β-tetrazol-5-yl) sulfopropyl thio- -1,2,3,4-tetrazole, colorless prisms;

1-fensh1-5- (3-benzylcarbonylpropyl) thio-, 2,3,4-tetrazole, pale yellow liquid, 1.5948;

1-phenyl-5- (3-isobutyrylpropyl) thio-1,2,3, -4-tetrazole, colorless liquid, 1.5552;

1-phenyl-5- (3-cyclopentylcarbonyl-propyl) thio-1,2,3,4-tetrazole, crystalline powder, m.p. 56.5-57.5 ° C (methanol-water);

1-fensh1-5- (3-butyrylpropyl) thio- -1,2,3,4-tetrazole, pale yellow liquid, 1.5640;

1-phenyl-5- (2-cyclohexylcarbonyl ethyl) thiomethyl-1,2,3,4-tetrazole, a colorless liquid, n "1.5627; at

1-phenyl-5- (2-cyclohexylcarbonyl-etyp thio-1,2,3,4-tetrazole, colorless liquid, n 1.5684;

1-fvSh1l-5- (3-pentanosh1propyl) thio--1,2,3,4-tetrazole; pale yellow liquid, PD 1,5502;

1-phenyl-5-3-heptanoylpropyl) tyo-I, 2,3,4-tetrazole, colorless liquid, Pp 1.5388;

1-phenyl-5- (5-cyclohexylcarbonyl-pentyl) thio-1,2,3,4-tetrazole, colorless needles, mp. 39.5-40, (ethyl acetate-ge to san).

Example 11. 1-Ch1-methyl-5- (4,4-α-ethylenedipoxyhexyl) thio-1,2,3,4-tetrazole (0.6 g) was dissolved in acetic acid (5 ml). To the solution is added

water (2., 5 ml) and concentrated hydrochloric acid (0.5 ml), a mixture of ki pt in a water bath for 1 h. Water was added to the reaction mixture, the mixture was extracted with chloroform. The chloroform solution is washed with water, saturated aqueous sodium bicarbonate, then saturated aqueous sodium chloride, and dried over magnesium sulfate. Chloroform is distilled off and the residue is purified by chromatography on coloic (Kieselgel, 60). The column was eluted with a mixture of benzene and ether (10: 1-methyl-5- (3-propionylpropyl) was obtained) thio-1,2,3,4-tetrazole (0.4 g) as a colorless liquid, n, 1, 5042.

Calculated,%: C, 44.84; H 6.59; N 26.15

Cgll).

Found,%: C 44.89; H 6.63; N 26.23.

Example 12. In accordance with example 11 receive:

1-methyl-5- (3-cyclohexylcarbonyl propyl) hyo-1,2,3,4-tetrazole, colorless liquid, Pp 1.5267;

1-methyl-5- (3-beneoylpropyl) thio--1,2,3,4-tetrazole, colorless needles (methanol-water, mp 57.5-58 ° C;

1-phenyl-5- (3-cyclohexylcarbonyl-propch1) thio-1,2,3,4-tetrazole, colorless granules (methanol-water), so pl. 57.5-58.5 ° C;

1-phenyl-5- (3-benzoylpropyl) thio--1,2,3,4-tetrazole, colorless granules (methanol-water), so pl. 71-72 C;

1-cyclohexyl-5- (3-cyclohexyl-carbonylpropyl) thio-1,2,3,4-tetra azole pale yellow liquid, p 1.5282

1-methyl-5-acetylthio-1,2,3,4-geth-razol colorless needles (methanol-ether), so pl. 3l C;

1-methyl-5-benzylmethylthio-1,2,3,4-tetrazole, colorless granules (methanol), m.p. 130.5-131.5 С:

1-methyl-5- (2-benzoyletsch1) thio-1,2, 3,4-tetrazole, colorless plates (ligroin), so pl. 70-80 ° C;

1-methylt5- (4-benzoylbutyl) thio-I, 2,3,4-tetrazole, colorless flakes (methanol-water), etc. 72-73.5 ° C;

1-methyl-5- (5-benzoylpentyl) thio- -1,2,3,4-tetrazole, colorless plates (hexane-ether), m.p.

44 ° C; 1-ytil-5- (3-acetylpropyl) thio-1, 2,3,4-tetrazole, colorless liquid, PD - I, 5194;

23

1-methyl-5- (3-pentanoylpropyl) thio--1,2,3, -4 tetrazole, colorless liquid, 1.5069;

I-methyl-5- (3 cyclopentylcarbonyl-propyl) thio-1,2,3,4-tetrazole, colorless liquid, n 1.5256,

Example 13. 1-Methl-5- (4,4-α-ethylenedioxy-4- (4-ethyl phenesh1) butsh1 tis-1,2,3,4-tetrazole (0.8 g) is dissolved in acetic acid (5 ml Water (2.5 ml) and concentrated hydrochloric acid (0.5 ml) are added to the solution, the mixture is boiled on a water bath for 1 h, water is added to the reaction mixture and the mixture is extracted with chloroform. the solution is washed with water, a saturated aqueous solution of sodium bicarbonate and then with a saturated aqueous solution of sodium chloride and dried over magnesium sulfate. Chloroform is distilled off, the residual is purified by chromatography on a Kiz column. Elgel 60). The column was eluted with a mixture of benzene-ether (10: 1) to obtain 1-methyl-5- 3- (4-ethylbenzoyl) npommj thio-1,2,3,4-tetrazol (0.5 g) in the form of colorless needles so pl. 68-69 C (hexane-ether)

N

Calculated 19.90

%: C 57.91; H 6.25;

Example 15. 1-Methyl-5- 4,4-α-ethylenedioxy-4- (2-pyridyl) butyl thio- -1,2,3,4-tetrazole (0.7 g) was dissolved in acetic acid (5 ml ). Water (2.5 ml) and concentrated hydrochloric acid (0.5 ml) are added to the solution, the mixture is boiled in a water bath for 1 hour. Water is added to the reaction mixture and the mixture is extracted with chloroform. The chloroform solution is washed with water, a saturated aqueous solution of sodium bicarbonate, then with a saturated aqueous solution of sodium chloride and dried over magnesium sulfate. Chloroform was distilled off and the residue was purified by column chromatography (Kieselgel 60). The column was eluted with a mixture of benzene and zfnr (10: 1) and the product was recrystallized from a mixture of hexane and ether, to obtain 1-methyl-5-s- (2-pyridyl carbonyl) pro, 2,3,4-tetrazole (0.5 g ) in the form of colorless needles, so pl. 73-75 C.

thirty

C, 4H,

Found N 19.81

Example

py 13 get

%: C 57.68; H 6.20;

35

40

Calculated, 7: С 50.17; H 4.97; N 26.60

С „Н„ NjOS

Found,%: C 50.12; H 4.97; S 26.90

Example 16. In Example 15, the following compounds were prepared:

1-methyl-5- 3- (2-thenoyl) fuch1 | thio-1,2,3,4-tetrazole, colorless needles (hexane - ether) so pl. 55-56 ° C;

1-methyl-5-3- (2-furoyl) propyl thio-1,2,3,4-tetrazole, colorless needles (hexane-ether), so pl. 41-42 ° C .;

1-methyl-5- 3- (5-methyl-2-thenoyl) Propyl thio-1,2,3,4-tetrazole, pale yellow needles (hexane-ethyl acetate), mp. 78-80 s;

    , 1-methyl-5-Сз- (5-chloro-2-thenoyl)

propyl thio-1,2,3,4-tetrazole; colorless - 50 propyl.thio-1,2,3,4-tetrazole; pale flakes (hexane-ethyl acetate, mp 107-108 ° C;

1-methyl-5- 3- (4-hydroxybenzoyl) saw thio-1,2,3,4-tetrazo, colorless needles (water), m.p. 128.5-129.5 ° C;

-methyl-5- 3- (2-naphtol) propyl thio-1,2,3,4-tetrazole, colorless prisms (ethanol), so pl. 118-120 ° C;

14. According to the example, the following compounds:

1-methyl-5- 3- (4-acetylaminobenzoyl) propyl thio-1,2,3,4-tetrazole, colorless needles (ethanol)., So pl. 170-172 ° C;

1-metsh1-5- 3 (3,4-dimethoxybenzoyl) propyl thio-1,2,3,4-tetrazole, colorless hexane-ethyl acetate prisms. m.p. 86-87 ° C;

1-methyl-5- 3- (4-chlorobenzoyl) propyl thio-1,2,3,4-tetrazole, colorless prisms (methanol-water), so pl. 139UO C;

1-methyl-5- 3- (4-methoxybenzoyl)

55

yellow needles (hexane-ethyl acetate), so pl. 91-92 ° C;

1-methyl-5-3- (2-pyrrolylcarboyl propyl thio-1,2,3,4-tetrazole, pale yellow prisms (hexane-ethyl acetate) mp 94-96 C;

1-metsh-5- 3- (2,5-dimethyl-Zfurr-yl) propyl thio-1,2,3,4-tetrazole,

24

24

1-methyl-5- 3- (benzsh1karbopsh1} propyl thio-1,2, 3,4-tetrazole, 25 colorless

for liquid, nj 1.5610;

1-methyl-5- 3 (| 5-phenylethylcarbonyl: propyl thio-1,2,3.4-tetrazole, colorless liquid, Hj, 1.5561.

Example 15. 1-Methyl-5- 4,4-α-ethylenedioxy-4- (2-pyridyl) butyl thio- -1,2,3,4-tetrazole (0.7 g) was dissolved in acetic acid (5 ml ). Water (2.5 ml) and concentrated hydrochloric acid (0.5 ml) are added to the solution, the mixture is boiled in a water bath for 1 hour. Water is added to the reaction mixture and the mixture is extracted with chloroform. The chloroform solution is washed with water, a saturated aqueous solution of sodium bicarbonate, then with a saturated aqueous solution of sodium chloride and dried over magnesium sulfate. Chloroform was distilled off and the residue was purified by column chromatography (Kieselgel 60). The column was eluted with a mixture of benzene and simple zfnr (10: 1) and the product was recrystallized from mixtures. si of hexane and ether, 1-methyl-5-z- (2-pyridsh1carbonip) pro-, 2,3,4-tetrazole (0.5 g) is obtained as colorless needles, mp. 73-75 C.

Calculated, 7: С 50.17; H 4.97; N 26.60

propyl, thio-1,2,3,4-tetrazole; pale

yellow needles (hexane-ethyl acetate), so pl. 91-92 ° C;

1-methyl-5-3- (2-pyrrolylcarboyl propyl thio-1,2,3,4-tetrazole, pale yellow prisms (hexane-ethyl acetate) mp 94-96 C;

1-metsh-5- 3- (2,5-dimethyl-Zfurr-yl) propyl thio-1,2,3,4-tetrazole,

25

colorless plates (jreKcaH protoy ether), tp, 67-68,

I-methyl-5- {3- (3 4-dihydrocarbo styrene-6-yl) carbonylT propylj thio- -1,2,3,4-tetrazole, colorless needles (ethanol), mp. 183-190 ° C;

1-methyl-5- 3- (1 H "etyl-3,4-digi rocarbostyrol-6-yl) carbonyl propyl thio - ,, 3,4-tetrazole, colorless and ly (hexane-ethyl acetate), mp. 110- U3.5 ° C.

Example 17

A. J-MeTmr-S-MepKanTO-l, 2,3,4-β-tetrazole (0.01 mol), potassium carbonate (0.015 mol) and "; -chloroacetone (0.015 mol) was added to acetone (60 ml) and the mixture was heated under reflux with stirring for 2 hours. The reaction mixture was evaporated to dryness under reduced pressure, the residue was dissolved in chloroform. Insoluble substances are filtered off. The filtrate is concentrated under reduced pressure, the residue is felt using a column chromatography (Kieselgel 60), α-eluent: benzene-ether mixture (lO: l the product is recrystallized from a mixture of methanol and ether, to obtain 1-methyl-5-acetylmethylthio- 1,2,3,4-tetrazole (yield 48%) in vi

de colorless needles, so pl. 31 C.

Calculated,%: C 34.87; H 4.68} N 32.54

CyHgN OS

Found,%: C 34.43; H 4.54; N 38.83.

B. 5 Mercapto-1,2,3,4-tetrazole (1 g), potassium carbonate (2 g) and ai — chloroacetone (1.4 g) is added to acetone (50 ml), the solution is boiled, reflux with stirring for 2 hours. The reaction mixture is evaporated to dryness under reduced pressure and the residue is dissolved in chloroform. Insoluble materials are filtered off and the filtrate is evaporated under reduced pressure. The residue is purified on a column (Kieselgel 60, eluent: benzene-ether (10: 1), 5-acetylmethylthio-1, 2,3,4-tetrazole (0.4 g) is obtained as a colorless liquid.

N.1 number,%: C 30.37; H 3.82; N 35.42

Found,% C 30.35; H 3, .81; N 35.50.

2324

26

Example 18. According to Example 17A, the following compounds are prepared;

1-methyl-5- (3-benzoylpropyl) thio- -1,2,3,4-tetrazole, colorless needles 5 (methanol-water), so pl. 57.5-58 seconds;

1-methyl-5- (3-cyclohexylcarbonyl-propyl) thio-1,2,3,4-tetrazole, colorless liquid, p 1.5267

1-phenyl-5- (3-cyclohexylcarbonyl-0-propyl) thio-1,2,3,4-tetrazole, colorless granules (methanol-water), mp. 57.5-58.5 ° C;

1-phenyl-5- (3-benzoylpropyl) thio--1,2,3,4-tetrazole, colorless granules, (methanol-water), so pl. 71-72 C;

1-cyclohexyl-5- (3-cyclohexyl-carbonash1propyl) thio-1,2,3,4-tetrazole, a pale yellow liquid, nj 1.5282;

1-metschg-5- (3-propionylpropyl) thio

five

0

-1,2,3,4-tetrazole, colorless liquid, p 1.5042;

; I-methyl-5-benzoylmethylthio-1,2, .3,4-tetrazole, colorless granules 5 (methanol) so pl. 130.5-131.5 ° C;

, 1-methyl-5- (2-benzoyl ethyl) thio--1,2,3,4-tetrazole, colorless plates of ligroin, m.p., 8-80 ° C; 1-methyl-5- (4-benzoylbutyl) thio

"IO

PE

-1,2,3,4-tetrazole, colorless flakes (methanol - water), so pl. 72-73.5 C;

1-methyl-5- (5-benzoylpentyl) thio -1,2,3,4-tetrazole, colorless plates (hexane-ether), mp, 44 ° C;

1-methyl-5- (3-acetylpropyl) thio-i, 2,3,4-tetrazole, colorless liquid 1,5194;

1-methyl-5- (3-pentanoylpropyl) thio -1,2,314-tetrazole, colorless liquid, p 1.5059;

1-methyl-5- (3-cyclopentylcarbonyl-prop1) thio-1,2,3,4-tetrazole, colorless liquid, 1.5256.

Example 19. 1-Methyl-5-mercapto-1,2,3,4-tetrazole (1.2 g), potassium carbonate (2.1 g) and 3-chloropropyl-4-ethyl phenyl ketone (3.2 d) is added to acetone (50 ml), the mixture is refluxed for 2 h. The reaction mixture is evaporated to dryness under reduced pressure. The residue is dissolved in chloroform. Insoluble substances are filtered off. The filtrate is evaporated under reduced pressure, and the residue is purified by chromatography on a column (Kieselgel 60), eluent: a mixture of benzene and ether (10: I), the product

recrystallized from a mixture of hex and ether, to obtain 1-methyl-5-3- (4-ethylbenzoyl) propyl thio- -1,2,3, A-tetrazole (49% yield) as colorless needles, t. PC. 68-BE With

Calculated,%: C 57.91; H 6.25; N 19.90.

C ,, H,

Found,%: C 57.78; H 6.23; N 19.71.

Example 20. According to Example 19, the following compounds were prepared:

1-methyl-5- (4-acetylaminobenzoyl) propyl thio-1,2,3,4-tetrazole, colorless needles (ethanol), so pl. 170-172 ° C;

1-methyl-5-H- (3,4-dime sibenzoyl) propyl thio-1,2,3,4-tetrazole are colorless prisms (hexane-ethyl acetate so pl. 86-87 C ;.

1-methyl-5-Z- (4-chlorobenzoyl) propyl thio-1,2,3,4-tetrazole, colorless prisms (methanol-water), so pl. 139-140 ° C;

1-methyl-5-W- (4-butoxybenzoyl) propyl thio-1,2,3,4-tetrazole, colorless prisms (ethanol), so pl. 73.5-75.5 ° C;

1-methyl-5- 3- (2-methoxybenzoyl) propyl thio-1,2,3,4-tetrazole colorless needles (ethyl acetate-hexane); m.p. 98-100 ° C;

1-methyl-5-W- (3-methoxybenzoyl) propyl thio-1,2,3,4-tetrazole, colorless plates (ether-hexane), mp, 48-49 ° C;

1-meth-1-5- 3- (4-methoxybenzoyl) propyl thio-1,2,3,4-tetrazole, colorless flakes (hexane - ethyl acetate, mp 107-108 ° C;

1-methyl-5-Z- (4-hydroxybenzoyl) propyl thio-1,2,3,4-tetrazole, colorless needles (water), so pl. 128.5-129.5 ° С

Example 21. 1-Methyl-5-mercapto-1,2,3,4-tetrazole (1.2 g), potassium carbonate (2.1 g) and 3-chloropropyl-2-pyridyl ketone (2.8 d) was added to acetone (50 ml), the mixture was heated under reflux for 2 hours. The reaction mixture was evaporated to dryness under reduced pressure, the residue was dissolved in chloroform. Non-soluble substances are filtered off; the filtrate is concentrated under reduced pressure. The residue is purified by chromatography on a column (RS-60) eluent: benzene simple ether 10: 1) and the product is recrystallized from a mixture of hexane and ether to give 1-methyl 1- (2-pyridylcarbonyl) propyl thio -1.2,3 , 4-tetrazole (yield 50%) in the form of colorless needles, so pl. 73-75 C. Calculated,%: C 50, 17; H 4.97; N 26.60

C ,, H ,, N50S

Found,%: C 50.21; H 4.89; N 16.72

Example 22. In accordance with Example 21, the following compounds were prepared:

1-methyl-5-3- (2-thooyl) propyl thio- -1,2,3,4-tetrazole, colorless needles (hexane-ether), m.p. 55-56 ° C;

1-methyl-5-3- (2-furoyl) propyl thio- -1,2,3,4-tetrazole, colorless needles (hexane-ether), m.p. 41-42 ° C;

1-methyl-5- 3- (5-methyl-2 enoyl) propyl thio-1,2,3,4-tetrazole, pale yellow needles (hexane-ethyl acetate), mp. 78-80 ° C;

1-methyl-5- 3- (5-chloro-2-thenoyl) propyl thio-1,2,3,4-tetrazole j pale yellow needles (hexane-ethyl acetate), mp. 91-92 ° C;

1-methyl-5-z- (2-pyrrodylcarbonyl) propyl thio-1,2,3,4-tetrazole, pale yellow prisms (hexane-etipacetate), mp. 94-96 ° C:

1-methyl-5-z- (2,5-dimethyl-3-furo-ip) propyl thio-1,2,3,4-tetrazole, colorless plates (hexane-ether), so pl. 67-68.5 C;

1-methyl-5- 3 (3 J 4-dihydrocarbostyryl-6-yl) carbonyl propyl thio- 1,2,3,4-tetrazole, colorless needles (ethanol), m.p. 188-190 ° C;

-1-methyl-5- 3-C (-methyl-3,4-dihydrocarbostyryl-6-yl) carbonyl propyl thio-1,2,3,4-tetrazole, colorless needles hexane-ethyl acetate, mp. 110- P8,5 C;

1-methyl-5-z- (5-methoxycarbonyl-2g-furoyl) propyl thio-1,2,3,4-tetrazole, colorless needles (hexane-ethyl acetate), mp. 96-97 0.

Example 23, 1-Methyl-5-gmer-capto-1,2,3,4-hetrazole (1.2 g), potassium carbonate (2.1 g) and 3-chloropropyl-4-methyl-5. -thiazolyl ketone (3.1 g) was added to acetone (50 ml), the mixture was heated under reflux for 2 hours with stirring. Reactionary. the mixture is evaporated to dryness with reduced

pressure and the residue is dissolved in chloroform. Insoluble substances are filtered off and the filtrate is evaporated under reduced pressure. The residue is purified by chromatography on a column (Kieselgel 60, eluent: benzoate ether 10 J-1), the product is recrystallized from a mixture of hexane and ether, to give 1-methyl-5- (4-methylene 1-5- tyazolylcarbonyl) propyl thio-1,2,3,4-tetrazole {2.6 g) as colorless needles, mp. 64-65 0. EXAMPLE 24. According to Example 23, 1-methyl-5-3- (5-carboxy-2-furoyl) propyl thio-1,2,. 3 4-tetrazole in the form of colorless prisms (hexane-ethyl acetate), so pl. 154-157 seconds

Example 25. 1-Methyl-5-mercapto-1,2,3,4-tetrazole (1.2 g), potassium carbonate (2.1 g) and 3 chloropropyl -2 -2-naphtsch ketone (3.5 g ) Dbbavl to acetone (50 ml), the mixture was heated under reflux with stirring for 2 hours. The reaction mixture was evaporated to dryness under reduced pressure, and the residue was dissolved in chloroform. Insoluble substances are filtered off. The filtrate is evaporated, the residue is purified by column chromatography (Kieselgel 60, eluent: 10: 1 benzene ether) and the product is recrystallized from ethanol to give 1-methyl-5-H- (2-naphthoyl) propyl thio-1,2, - 3,4-tetrazole (yield 51%) as colorless prisms, mp. 118-120 C.

Calculated,%: C, 61.52; H 5.6 {N 17.94. h. C, 6H, gN, OS

Found,%: C 61.59; H 5.08; N 18.06

Example 26. 1-Methyl-5-mercapto-1,2,3,4-tetrazole (1.2 g), potassium carboxylate (2.1 g) and 3-chloro-proshbenzyl ketone (2.9 g) are added the mixture is boiled under acetone (50 ml) and the mixture is heated under reflux with stirring for 2 hours. The reaction mixture is evaporated to dryness under reduced pressure, the residue is dissolved in chloroform. Insoluble substances are filtered off. The filtrate is evaporated under reduced pressure. The residue is purified by column chromatography (Kieselgel 60, eluant: benzene-ether 10: 1 |, 1-methyl-5- (3-benzylcarbonyl) propyl thio-1,2,3,4-tetrazole is obtained (yield 50 %) at

five

five

2S D

as a colorless liquid, p 1.5310.

Calculated,%: C 56.50; H 5.64; N 20.27

C ,, H, jN40S

Found,%: With 56,40; H 5.83; N 20.17.

Example VII with an example

27. In accordance with 27, 1-methyl0-5-3-C-phenethylcarbonyl) propyl thio--1,2,3,4-tetrazole is obtained in the form of a colorless liquid, 1.5561.

P i m i p 28. 1-Methyl-5-chloro-rl, 2,3,4-tetrazole (2.4 g) is dissolved

5 in ethanol (30 ml). Thiourea (1.5 g) was added to the solution and the mixture was heated under reflux for 2 hours; Z-bromproshshtstsikloketone (4.7 g) and 10% aqueous solution

0 Sodium hydroxide (10 ml) was added to the mixture and heated under reflux for an additional 3 hours. Ethanol was distilled off, and water was added to the residue. The mixture is extracted

5 chloroform. The chloroform solution is washed with water and then with saturated sodium chloride and dried with magnesium sulfate. Chloroform is distilled off, and the residue is purified by chromatography on a column (Wacogel C-200 eluent: chloroform) to give 1-methyl-5- (5-cyclohexylcarbonyl dipropyl) thio-1, 2,3,4-tetrazole (1.4 g) as a colorless liquid, n "1.5267.

Example 29. In accordance with Example 28, the following compounds were prepared:

1-methyl-5- (3-propionylprosh) thio- -1,2,3,4-tetrazole, colorless liquid

75

bone, 1,

-methyl-5- (3-benzoylpropsh1) thio- -1,2,3,4-tetrazole, colorless needles (methanol-water), so pl. 57,

1-phenyl-5-g (3-cyclohexylcarbonyl-propyl) thio-1,2,3,4-tetrazole, colorless granules (methanol-water), so pl. 57.5-58,

1-phenyl-5- (3-benzoylpropyl) thio--1,2,3,4-tetrazole, colorless granules (methanol-water), so pl. 71-72 C;

1-cyclohexyl-5- (3-cyclohexylcarboylpropyl) -thio-1,2,3,4-tetrazole is a pale yellow liquid,

1-methyl-5-acetylmethyl-ITO-1,2,3,4-tetrazole, colorless needles (methanol-ether), mp- 31. C;

1-methyl-5-benzoylmethylthio-1,2,3,4-tetrazole, colorless granules (methanol, mp. 130.5-131,

1-methyl-5- (2-benzoylethyl) thio-1,2, 3,4 tetrazole, colorless plates (ligroin), so pl. 78-80 ° C;

1-methyl-5- (4-benzoylbutyl) thio- -1,2,3,4-tetrazole, colorless flakes (water), so pl. 72-73.5 ° C;

1-metshg-5- (5-ben zoylpentyl) thio--1,2,3,4-tetrazole, colorless plates (ether), so pl. 44 ° C;

1-methyl-5- 3 (4-acetylaminobenzoyl) propyl yew-1,2,3,4-tetrazole, colorless needles (ethanol), so pl. 170-

1-methyl-5-z- (3,4-dimethoxybenzoyl) propyl thio-1,2,3,4-tetrazole, colorless prisms (hexane-ethyl acetate, mp 86-87 s;

1-methyl-5-H- (4-chlorobenzoyl propyl thio-1,2,3,4-tetrazole, colorless prisms (methanol-water, mp 139-

1-methyl-5 - h- (4-methoxybenz6sh1) propyl thio-1,2,3,4-tetrazole, colorless flakes (hexane-ethyl acetate), mp. 107-108 ° C;

1-methyl-5-z- (4-hydroxybenzoyl) propyl thio-1,2,3,4-tetrazole, colorless needles (water), so pl. 128.5-129,

1-methyl-5- 3- (2-naphthoyl) propyl thio-1,2,3,4-tetrazole, colorless prisms (ethanol), so pl. 118-120 ° C;

1-methyl-5- (3-beisylcarbonyl) -propyl} thio-1,2,3,4-tetrazole, colorless liquid, PD, 1.5610;

1-methyl-5-W- (p-phenethylcarbonyl) propyl thio-1, 2,3,4: -tetrazol, colorless liquid, Pr 1.5561.

Example 30. 8- (1-Methyl-1, 2, 3,4-tetrazol-5-yl) isothiourea hydrochloride (1.9 g) was dissolved in ethanol (50 ml). A 10% aqueous solution of sodium hydroxide (5 ml) and 3-chloropropyl-2-pyridyl ketone (1.6 g) were added to the solution, the mixture was heated under reflux for 2 hours. Ethanol was distilled off. water is added. The mixture is extracted with chloroform. The chloroform solution is washed with water and a saturated aqueous solution of sodium chloride and dried over magnesium sulfate. Chloroform was distilled off, the residue was purified by column chromatography (C-200 Vakogel, chloroform as eluent), and the product was recrystallized from a mixture of hexane and ether. 1-methyl-5-Z- (2-pyridylcarbonyl) propyl thio-1,2,3,4-tetrazole (0.5 g) is obtained as colorless needles, mp. 73-75 C.

Example 31. According to example 30, the following compounds were prepared:

1-methyl-5- 3- (2-thenoyl) propyl thio -1,2,3,4-tetrazole, colorless needles (hexane-ether), so pl. 55 - 5b with;

1 - "Etil-5- 3- (2-Eight 1) propyl thio -1, 2,3,4-tetrazole, colorless needles (hexane-ether), so pl. 41 - 42 C;

1-methyl-5- З- (5-methyl-2-; tenocl) propyl thio-1,2,5,4-tetrazole, pale yellow needles (hexane-ethyl acetate), mp. 78-80 ° WITH;

1-methyl-5- 3- (5-m-t-chloro-2-teno-propyl-thio-1,2,3,4-tetrazole; pale yellow needles (hexane-ethyl acetate), mp.

1-methyl-: 5- 3- (2-pyrrolylcarb6inyl propyl thio-1,2,3,4-tetrazole, pale yellow prisms (hexane-ethyl acetate), mp 94-96 ° C;

1-methyl-5-3- (2,5-dimethyl-3-furoyl) propyl thio-1,2,3,4-tetrazole, colorless plates (ether), so pl. 67-68 ° C;

1-metsshg-5-Z- (3,4-dihydrocarboxystyrsh1-6-yl) carbonyl propyl thio- -1,2,3,4-tetrazole, colorless needles (ethanol), so pl. 188-190 ° C;

1-methyl-5-z- (1-methyl-3,4-dihydrocarbostyryl-6-yl) propyl thio-1,2,3, -tetrazol, colorless needles (hexane-ethyl acetate), m.p. , 5 s.

Example 32. 1-Methyl-5-chloro--1,2,3,4-tetrazole (1.4 g) and 3-mercaptopropylcyclohexyl ketone (2.9 rj is dissolved in methanol (50 ml), to the solution is added potassium hydroxide (0.8 g). The mixture is boiled under reflux for 5 hours. Methanol is distilled off and water is added to the residue. The mixture is extracted with chloroform. The chloroform solution is penetrated with dilute aqueous sodium hydroxide, water and a saturated aqueous solution of chloride sodium and dried with sodium sulfate. Chloroform is distilled off; the residue is purified by column chromatography (Wacogel — C-200, eluent: chlorofor m), 1-methyl-5- (3-cyclohexylcarbonippropyl) thio-1,2,3,4-tetrazole (0.6 g) is obtained as a colorless liquid, n "1.5267.

Example 33. In accordance with Example 32, the following compounds were prepared:

33

1-methyl-5- (3-propionylpropyl) thio- -1,2,3,4-tetrazole, colorless liquid, - 1.5042;

1-methyl-5- (3-benzoylpropyl) thio- 1,2,3,4-tetrazole, colorless needles (methanol-water), mp, 57.5-58 ° C

1-phenyl-5- (3-cyclohexylcarbonyl-prop 1) thio-1,2,3,4-tetrazole, colorless granules (methanol-water), so pl. 57.5-5.8 С;

1-phenyl-5- (3-benzoylpropyl) thio--1,2,3,4-tetrazole, colorless granules (Meuanol-water), so pl. 71-72 ° C}

1-cyclohexyl-5- (3-cyclohexyl-carbonylpropyl) thio-1,2,3,4-tetrazole, pale yellow liquid, p - 1.5282;

1-methyl-5-acetylmethylthio-1,2,3,4-g-tetrazole, colorless needles (methanol-water), mp, 31 ° C;

1-methyl-5-benzoylmethylthio-1,2,3,4-tetrazole, colorless granules (methanol), m.p. 130.5-131.5 ° C;

1-5methyl-5- (2-benzoylethyl) thio-1,2 3,4-tetrazole, colorless. Plates (ligroin), mp, 78-80 ° C;

1-methyl-5- (4-benzoylbutyl) thio- -1,2,3,4-tetrazole, colorless flakes (methanol-water), so pl. 72-73,

1-methyl-5- (5-benzoylphenyl) thio- -1,2,3,4-tetrazole, colorless plates (hexac-ether) m.p. 44 ° C;

1-methyl-5-3- (4-acetylaminobenzo: yl) propyl thio-1,2,3,4-tetrazole, colorless needles (ethanol), mp. 170121232434

1-methyl-5- 3- (-phenethylcarbonyl)

ten

15

20

25

..

1-methyl-5- 3- (3,4-dimethoxybenzoyl) is stitched with thio-1,2,3,4-tetrazole, colorless prisms (hexane-ethyl acetate), mp, 86-87 ° C;

1-methyl-5-W- (4-chlorobenzoyl) propyl thio-1,2,3,4-tetrazole, colorless prisms (methanol-water), mp, 139-140 ° C;

1-methyl-5 -3- (4-methoxybenzoyl) propyl thio-1,2,3,4-tetrazole; non-flakes (hexane-ethyl acetate),

t.mi. 107-108 ° C; I

1-methyl-5- 3- (4-hydroxybenzoyl propyl thio-1,2,3,4-tetrazole, colorless needles (water), mp, 128.5-129, 1-methyl-5-3. (( 2-naphthoyl) propyl thio-1,2,3,4-tetrazole, colorless

(ethanol), so pl. P8-120 C;

propyl thio-1,2,3,4-tetrazole, colorless to liquid, 1.5561,

Example 34, 1-Methyl-5-chloro-1, 2, 3,4-tetrazole (1.4 g) and 3-mercap topropyl-2-pyridyl ketone (1.8 g) are dissolved in methanol (100 mp) . Sodium hydroxide (0.6 g) is added to the solution and the mixture is heated under reflux for 3 hours. Methanol is distilled off and water is added to the residue. The mixture is extracted with chloroform. The chloroform solution is washed with an aqueous solution of sodium hydroxide, water and a saturated aqueous solution of sodium chloride and dried, sodium sulfate. Chloroform is distilled off, the residue is purified by column chromatography / Wacogel C-200, eluant: chloroform the product is recrystallized from hexane / ether. I get 1-methyl-5-z- (2-pyridylcarbonyl) propyl thio-1, 2,3,4-tetrazole (0.2 g) as colorless needles, so pl. 73-75 C.

Example 35. According to Example 34, the following compounds 1-methyl-5- 3- (2-tenryl) propyl are obtained.

-1,2,3,4-tetrazole, colorless needles, 30 (hexane-ether), m.p. 55-56 ° C;

1-methyl-5- 3- (2-furoyl) propyl thio-1,2,3,4-tetrazole, colorless needles (hexane-ether), so pl. 4135 42 C; ,

1-methyl-5-z- (5-methyl-2-tenoyl) propyl thio-1,2,3,4-tetrazole, pale yellow needles (hexane-ethyl acetate), mp, 78-80 ° C;

O1-methyl-5- 3- (6-chloro-2-thenoyl) pro

drank thio-1,2,3,4-tetrazole, pale yellow needles (hexane-ethyl acetate), t, mp, 91-92 s;

1-methyl-5- 3- (2-pyrrolylcarbonyl) 45 propyl thio-1,2,3,4-tetrazole, pale yellow prisms (hexane-ethyl acetate), mp, 94-96 ° C;

1-methyl-5-3- (2,5-dimethyl-3-fluoroyl) propyl thio-1,2,3,4-tetrazole, 50 colorless plates (hexane-ether), m.p. 67-68.5 ° C;

1-methyl-5- f3- (3,4-dihydrocarboxystyryl-6-yl) carbonyl propyl thio- -1,2,3,4-tetrazole, colorless needles 55 (ethanol), t, mp, 188-190 WITH;

1-methyl-5- {3- (1-methyl-3,4-dihydrism,

1-methyl-5-3- (benzylcarbonyl) propyl thio-1, 2,3,4-tetrazole, colorless rocarbosterine 1-8-yl) carbonyl propyl liquid, D 1.5610; THoJ-1,2, -3, 4-tetrazole, colorless

propyl thio-1,2,3,4-tetrazole, colorless liquid, 1.5561,

Example 34, 1-Methyl-5-chloro-1, 2, 3,4-tetrazole (1.4 g) and 3-mercaptopropyl-2-pyridyl ketone (1.8 g) are dissolved in methanol (100 mp ). Sodium hydroxide (0.6 g) was added to the solution and the mixture was heated under reflux for 3 hours. Methanol was distilled off and water was added to the residue. The mixture is extracted with chloroform. The chloroform solution is washed with an aqueous solution of sodium hydroxide, water and a saturated aqueous solution of sodium chloride and dried, with sodium sulfate. Chloroform is distilled off, the residue is purified by column chromatography / Wacogel C-200, eluent: chloroform) the product is recrystallized from a mixture of hexane and ether to give 1-methyl-5-3- (2-pyridylcarbonyl) propyl thio-1, 2 , 3,4-tetrazole (0.2 g) as colorless needles, so pl. 73-75 C.

Example 35. According to Example 34, the following compounds were prepared: 1-methyl-5- 3- (2-tenryl) propyl thio-1, 2,3,4-tetrazole, colorless needles, (hexane-ether), m.p. 55-56 ° C;

1-methyl-5- 3- (2-furoyl) propyl thio-1,2,3,4-tetrazole, colorless needles (hexane-ether), so pl. 4142 С; ,

1-methyl-5-z- (5-methyl-2-tenoyl) propyl thio-1,2,3,4-tetrazole, pale yellow needles (hexane-ethyl acetate), mp, 78-80 ° C;

1-methyl-5- 3- (6-chloro-2-thenoyl) propyl thio-1,2,3,4-tetra azole, pale yellow needles (hexane-ethyl acetate), mp, 91-92 s;

1-methyl-5- 3- (2-pyrrolylcarbonyl) propyl thio-1,2,3,4-tetrazole, pale yellow prisms (hexane-ethyl acetate), mp, 94-96 ° C;

1-methyl-5-3- (2,5-dimethyl-3-fluorophenyl) propyl thio-1,2,3,4-tetrazole, colorless plates (hexane-ether), mp. 67-68.5 ° C;

1-methyl-5- f3- (3,4-dihydrocarbostil-6-yl) carbonyl propyl thio- -1,2,3,4-tetrazole, colorless needles (ethanol), t, mp, 188-190 ° C ;

1-methyl-5- {3- (1-methyl-3,4-dihydrocarboxy1-8-yl) carbonyl propyl-THoJ-1,2, -3,4-tetrazole, colorless

35

needles (hexane-ethyl acetate), so pl. 110- 113.5 ° C.

Example 36. 4-Chlorobutyrophenone (1.8 g) and thiourea (0.8 g) are dissolved in ethanol (50 ml), the solution is heated under reflux for 2 hours. To the mixture is added 1-methyl -5-chloro-1,2,3,4-tetrazole (1.2 g) and a 10% aqueous solution of sodium hydroxide (5 ml); the mixture was additionally heated under reflux for 3 hours. Ethanol was distilled off. and water is added to the residue. The mixture is extracted with chloroform. The chloroform solution is washed with water, a saturated aqueous solution of sodium chloride and dried over magnesium sulfate. Chloroform is distilled off. The residue is purified by chromatography on a column (C-200 Wacogel, eluent: chloroform), the product is recrystallized and mixtures of methanol and water are obtained. 1-methyl-5- (3-benzoylpropyl) thio-1,2,3,4- tetrazole (0.3 g) in the form of colorless needles, so pl. 57.5-58 C.

Example 37. According to Example 36, the following compounds were prepared:

1-methyl-5- (3-propionylpropyl) thio -1,2,3,4-tetrazole, colorless liquid, p 1.5042;

1-methyl-5- (3-cyclohexylcarbonyl-propyl) thio-1,2,3,4-tetrazole, a colorless liquid, Pr 1.5267;

1-phenyl-5- (3-cyclohexylcarbonyl- Tr1propyl) thio-1, 2,3,4-tetrazole, colorless granules (methanol-water), mp. 57.5-58 ° C;

1-phenyl-5- (3-benzoylpropyl) thio- -1,2,3,4-tetrazole, colorless granules (methanol-water), so pl. 71-72 C;

1-cyclohexyl-5- (3-cyclohexylcarbenylpropyl) thio-1,2,3,4-tetrazole, pale yellow liquid, n | f l, 5282

1-methyl-5-acetylmethylthio-1,2,3,4-tetrazole, colorless needles (methanol-ether), m.p.

1-methyl-5-benzoylmethylthio-1,2,3,4-tetrazole, colorless granules, (meth tanol), so pl. 130.5-131.5 ° C;

1-methyl-5- (2-benzoylethyl) thio--1,2,3,4-tetrazole, colorless plates (ligroin), so pl. 78-80 ° C;

1-methyl-5- (4-benzoylbutyl) thio- -1,2,3,4-tetrazole, colorless flakes (methanol-water), so pl. 72-73.5 C;

1-methyl-5- (5-benzoylpentyl) thio-l, 2,3,4-tetrazole, colorless plates (hexane - ether) ,. m.p. 44 C;

1232436

1-methyl-5- 3- (4 acetylaminobenzoyl) propyl thio-1,2,3,4-tetrazole, a colorless needle (etchnol), mp. 170-172 ° C;

51-methyl-5-z- (3,4-dimethoxybenzo-

til-1, 2,3,4-tetrazole, colorless prisms (hexane-ethyl acetate), so pl. 86-87 ° C;

1-methyl-5- 3- (4-chlorobenzoyl) propyl sawllo-1,2,3,4-tetrazole, colorless prisms (methanol-water), so pl. 139-140 ° C;

1-methyl-5-z- (4-methoxybenzoyl) propyl | thio-1,2,3,4-tetrazole, 15-color flakes (hexane-ethyl acetate), mp. 107-108 ° C;

1 -: methyl 4-z- (4-hydroxybenzoyl) propyl thio-1,2,3,4-tetrazole, colorless needles (water), so pl. 128.5-129.5 ° C; 201-methyl-5- 3- (2-naphthoyl) propyl

thio-1,2,3,4-tetrazole, colorless prisms, (ethanol), mp, 118-120 ° C;

1-methyl-5-z- (benzylcarbonyl) propyl thio-1, 2,3,4-tetrazole, 25 colorless liquid, PU 1.5610;

1-methyl-5-.3- (p-phenethylcarbonyl) prptilTtio-1,2,3,4-tetrazole,

I

thirty

2С 5

colored liquid, p 1,556K

Example 38, 3H-Chloropropyl-2-pyridyl ketone (1.8 g) and thiourea (0.8 g) were dissolved in ethanol (50 ml) and the solution was heated under reflux with stirring for 2 hours. To the mixture was added 1-methyl-535-chloro-1,2,3,4-tetrazole (1.2 g) and 10% g aqueous sodium hydroxide (5 ml, the mixture is heated under reflux for 3 hours. After evaporation of ethanol under reduced

 pressure is added to the residue water. The mixture is extracted with chloroform, the extract is washed with water and a saturated aqueous solution of sodium chloride, and dried over magnesium sulfate.

5 After distilling off the chloroform residue

purified by chromatography on a column (Wacogel-C-200, eluting agent: chloroform), followed by recrystallization from a mixture of hexane 5 ether, to obtain 1-methyl-5-. {{3- (2-pyridylcarbonsh1) propyl thio- 1,2,3,4-tetrazole (0.2 g) in the form of colorless crystals, mp; 73-75 C.

55 Example 39. In Example 38, the following compounds were prepared:

1-methyl-5- 3- (2-ten6yl) propyl | thio. -1,2,3,4-tetrazole, colorless needles

37

(hexane-ether), m.p. 55-56 ° C;

1-methyl-5-3- (2-furo-ip) propyl 1 thio-1, 2,3,4-tetrazole, colorless needles (hexane-ether), mp, 41-42 ° C

1-metshg5-z- (4-methyl-2-thenoyl) propyl thio-1,2,3,4-tetrazole, pale yellow needles (hexane-ethyl acetate), so pl. 78-80 ° Cj

1-methyl-5- 3- (5-chloro-2-tenoyl) -propylthio, 2,3,4-tetrazole, pale yellow needles (hexane-etipacetate), m.p. 91-92 С:

1-methyl-5- 3- (2-pyrrolylcarbonyl) propyl thio-1,2,3,4-tetrazole, pale yellow prisms (hexane-ethyl acetate), m.p. 94-96 ° C;

1-methyl-5- | 3- (2,5-dimethyl-3-furoyl)) thio-1,2,3,4-tetrazol, colorless plates (hexane-ether), so pl. 67-68.5 C;

1-methyl-5- {3- (3,4-dihydrocarbostyryl-6-nl) carbonip} propyl thio- -1,2,3,4-tetrazole, colorless needles (ethanol), m.p. 188-190 ° C;

1-methyl-5-Z- (1-methyl-3,4-dihydrocarbostyryl-6-yl) is thio-1,2,3,4-tetrazol, colorless needles (hexane-ethyl acetate), mp . 1 10-1 13,5 ° C.

Example 40. 1-Methyl-5-mercap-to-1,2,3,4-tetrazole (2.4 g) and N-ethyl-N-propionyl-3-chloropropylamine (3.6 g) are dissolved in acetone (50 ml). Potassium carbonate (2.8 g) and iodide, potassium (0.1 g) are added to the mixture, and the mixture is heated under reflux for 4 hours. After distilling off the acetone, the residue is taken up in water and extracted with chloroform. The chloroform solution is washed with saturated aqueous sodium chloride. I - riem and dried with sodium sulfate. The chloropharm is distilled off, the residue is purified by column chromatography (neutral alumina, eluent-hexane) to give 1-methyl-5- 3- (N-ethyl-N-propionalalamio) propyl thio- -1,2,3, 4-tetrazole (1.2 g) as a pale liquid, 1.5220

Example 41. In Example 40, the following compounds were prepared:

1-methyl-5-z-N-propionylamino) propyl thio-1,2,3,4-tetrazole, pale yellow liquid, p 1.5311;

1-methyl-5-z- (H-ethyl-β-cyclohexiparbonylamino) propyl thio-1,2,3,4-tetrazole, colorless liquid, 1.5267;

12324.38

1-methyl-5- 3-N-cyclohexylcarbonylamino) propyl thio-1,2,3,4-tetrazole colorless flakes (hexane-ethyl acetate, mp. 86.5-88 ° C)

5 1-phenyl-5-z-N-ethyl-N-benzoylamino) propyl) thio-1,2,3,4-tetrazole, colorless liquid, Pp 1,5898;

1-phenyl-5-l2- (N-benzoylamino) propyl-thio-, 2,3,4-tetrazole, 10 colorless needles (hexane-ethyl acetate), mp. 105-107 ° C;

1-methyl-5- 3- (N-methyl-N-acetyl-amino) propyl thio-1,2,3,4-tetrazole, pale yellow prisms (hexane-ethyl-15 acetate), mp. 80-81 C;

.1-methyl-5- 3- (N-acetylamio) Propyl thio-1,2,3,4-tetrazole, free liquid, Id 1,5280;

1-methyl-5-ЗЧМ -methyl-M-tsnkohek-20 silkarboiyilamio propyl thio-1,2,3,4-tetrazol, colorless liquid, n j, Р 1,52685

1-methyl-5-z- (M-ethyl-M-cyclopentylcarbonylamino) propyl thio-1,2,3,4-25-tetrazole, colorless liquid, 1.5240;

1-methyl-5-t3- (N-cyclopentylcarbonylamino) propyl thio-1,2,3,4-tetrazole, colorless prisms (ether), 30 m.p. 70-72 С:

1-methyl-5- 2- (H-cyclohexylcarbonylamino) ethyl thio-1,2,3 j4-tetrazole, colorless needles (ether-ligroin), so pl. P5,5-116,5 С; 1-methyl-5- 3- (N-ethyl-N-benzoyl-amino) propyl thio-1,2,3.4-tetrazole, colorless liquid, P in 1,5454;

1-methyl-5-з-N- (2-pyridylcarbo-. -Nyl-amino propyl thio-1,2,3,4-tetrazole, brown liquid, 1.5782;

 1-methyl-5- {3-Methyl-M- {2-furylcarbonyl amio, propyl thio-1,2,3,4., -Tetrazol, colorless liquid, 1 1.5495;

1-methyl-5-f3-N- (2-furylcarbonyl) amino-propyl thio-1,2,3,4-tetrazole, colorless prisms (methanol-hexane), JJ so pl. 80.5-83 ° G;

1-methyl-5- 3- (M-benzosh I-N-propionylamino) propyl thio-1,2,3,4-tetrazole, colorless liquid, p 1.5538;

1-methyl-5-СЗ- (N-beisoylamino) propyl thio-1,2,3,4-tetrazole, colorless prisms (from ethanol-hexane), m.p. 76-77,

39

1-Methyl-5- 3- (N-hexanoylamino) propyl thio-1,2,3,4-tetrazole, pale yellow liquid, Pd 1.5133,

Example 42, 1-Methyl-5-mercapto-1,2,3,4-tetrazole (2.4 g) and H, N-diethyp-3-chloropropylamine (3.0 g) are dissolved in acetone (50 ml), potassium carbonate (2.8 g) and potassium iodide (0.1 g) are added to the mixture, the mixture is heated under reflux for 4 hours. After distillation of acetone, water is added to the residue and extracted with chloroform. The chloroform solution is saturated with an aqueous solution of sodium chloride and dried with sodium sulfate. After distilling off the chloroform, the residue is purified by chromatography on a column (neutral alumina, eluent-hexane) to give 1-methi-5-Gz- (N, n-diethylamins)) propyl thio- -1,2,3 4-tetrazole ( 1.09 g) in the form of a colorless liquid, u) 1,5040,

Example 43 In Example 42, the following compounds were obtained:

1-methyl-5-4- (M-benzyl-1-ethylamino) butyl-Thio-1,2,3,4-tetrazole, brown

Neva liquid, n

1.5520;

fc L1.

1 - ethyl-5- 3- (N, N-diethylamino) pro-thio-1,2,3,4-tetrazole, colorless

21

LIQUID, front 1,5120;

1-methyl-5-z- (5-metsh1 amino-1,2,3, tetrazol-1-sh1) propyl thio-1,2,3,4-tetrazole, colorless prisms (ethanol), mp, 122 -124.5 ° C.

Example 44, 1-Metsh1-5-mercapto-1,2,3,4-tetrazole (2.4 g) and 2-chloromethylpyridine (2.6 g) are dissolved in acetone (50 ml). Potassium carbonate (2.8 g) and potassium iodide (0.1 g) are added to the mixture, the mixture is refluxed for 4 hours. After distilling off the acetone, water is added to the residue and the mixture is extracted with chloroform. The chloroform solution is washed with a saturated aqueous solution of sodium chloride and dried over sodium sulfate. After distilling off the chloroform, the residue is purified by column chromatography (neutral alumina) to give 1-methyl-5- (2-pyridyl) methylthio-1,2,3,4-tetrazole (1.0 g) as colorless. prisms (ethanol), t, pl, 78-81 ° C,

Example 45 In Example 44, the following compounds were obtained:

1-methyl-5- (3-pyridyl) methylthio--1,2,3,4-tetrazole, colorless liquid, p 1.5845;

12324 0

1-methyl-5- (2-amnothiaz OL-4-IL) methylthio-1,2,3,4-tetrazole, colorless

ten

"five

20

25

needles (ethanol), t, pl, 114-118 Cj

1-methyl-5- (4-methoxynbenzyl) thio- -1,2,3,4-tetrazole, colorless liquid, 1.5878;

1-methyl-5-cyclohexane I methyl ethyl-1 -l. 2.3,4-tetrazole, colorless liquid;

bone, Pr 1,5298,

Example 46, 1-Methyl-4- (3- -chloropropyl) thio-1,2,3,4-tetrazole (1.9 g) and thiophenol (1.1 g) are dissolved in acetone (50 ml). Potassium carbonate (1.5 g) and potassium iodide (0.1 g) are added to the mixture, the mixture is refluxed for 3 hours. After the acetone is distilled off, water is added to the residue and the mixture is extracted with ether. The ether solution is washed with a dilute aqueous solution of sodium hydroxide, with a saturated aqueous solution of sodium chloride and dried with sodium sulfate. After distilling off the ether, the residue is purified by chromatography on a silica gel column (Kieselgel 60 eluent: benzene-chloroform 3: 1) to give 1-ethyl-5- (3-phenylthiopropyl) thio- - D, 2,3,4-tetrazole (2 , 5 g) in the form of a colorless liquid, p, 1.6008,

0

0

five

0

% C 49.60; H 5.30;

Calculated N 21.03

C ,, H ,, N, S2

Found-,%: C 49.34; H 5.12; N 20.85,

Example 47 In Example 46, the following compounds were obtained:

I-methyl-5- (3-cyclohexylthiopropyl) thio-1,2,3,4-tetrazole, colorless liquid, Pr 1.5433;

1-methyl-5-3- (2-pyridine) tyropropyl thio-1,2,3,4-tetrazole, light yellow liquid, p 1.6022;

1 -cyclohexyl-5- (3-ethylthiopropyl) thio-1,2,3,4-tetrazole, colorless liquid, Hj, 1.5433;

1-methyl-g5-Z- (1-methyl-1,2,3,4-β-tetrazol-5-yl) thiopropyl} thio-1,2,3,4-tetrazole, colorless prisms (ethanol), t , pl, 141.5-143.5 ° C;

1-methyl-5- 4- (1-methyl-1, 2,3,4-β-tetrazol-5-yl) thiobut1 thio-1,2,3,4-β-tetrazole, colorless needles (; tanol), t, pl, 122-123 C;

1-phenyl-5- 4- (1-phenyl-1,2,3,4-β-tetrazole 5-yl) thiobutyl thio-1,2,3,4-tetrazole, colorless needles (ethanol-chloroform) , t, pl, 127-1.28,5 ° C;

41

1-gmethyl-5- 3- (l-cyclohexyl--1,2,3, 4-tbtrazo-l-5-yl) thio-propyl | thio-1,, 4-tetraeol, light yellow liquid, front 1 | 5853}

1-nshg-5- 3-1-phenyl-, 2,3,4-gr-trazol t5-yl) thiopropyl | to- 1,2,3,4-tetrazole, needless needles (methanol-chloroform), mp, 81-82 C}

1-metsht-2-z- (1-methylnmidaeop-2- -yl) thiopropsch {1 thio-1,2,3,4-those traeol colorless needles (ether), so pl. 59.5-60.5 s.

Example 48.-1-MeTHn-S-CS- -c1-propyl), 2,3,4-tetra9ol (1.9 g) and 3-oxi 2-mercaptopyridine (1.3 g) is dissolved in acetone (50 ii ) potassium carbonate (1.4 g) and potassium iodide (0.1 g) are added to the mixture, the mixture is boiled under reflux for 5 hours. After the acetone is distilled off, water is added to the residue and the mixture is extracted with chloroform. The chloroform solution is washed with an aqueous solution of sodium chloride and dried over magnesium sulfate. After distilling off the chloroform, the residue is purified by chromatography (Kieselgel 60, eluent: chloroform-methanol), recrystallized from ethyl acetate-i-hexane, to obtain 1-methyl-5- 3- (3-hydroxy-2-pyridyl) thio propyl thio -1,2,3,4-tetrazole (1.2 g) as light yellow granules, so pl. 87.5-88.5 C.

Calculated,%; C 42.40; H 4.59; N24.73

C ,, H ,, N50S., Found

Found,%: C 42.29; H 4.70; H 24.66.

Example 49. In Example 48, the following compounds were prepared:

1-methyl-5- 2- (2-pyridyl) thiosyl thio-1,2,3,4-tetra9ol, colorless prisms, T.PL. 77-79 C (ethanol)}

1-met1SH-5-4- (2-pyridyl) thiobutyl. Thio-1,2,3,4-tetrazole, light yellow prisms, mp. 49-51, S c (ethanol-water);

1-methyl-5-5 (2-pyridip) thiopentyl thio-1,2,3,4-tetrazole, colorless liquid, Pd "1.5853;

1-methyl-5-f6- (2-pyridyl) thioheXyst thio-1,2,3,4-tetrazole, colorless prisms, m.p. 58-60 s (ethanol);

1-meth-1-5- 3- (4-methyl-2-pyrimidyl) thiopropyl thio-1,2,3,4-tetrazole, a continuous liquid, h 1.5853;

one

IS

25

"

20 p,

212324 (j2

1-methyl-2- 4- (1-methyl--1,2,3,4-tetrazol-5-yl) thiobium isobutyrebromide, white crystalline powder (acetone), m.p. 116.5-118.5 C 51-methyl-g5- 3- (2-benzimidazolshI) thiopropyl thio-1,2,3,4-tetrazole, colorless needles (ethanol), so pl. 137-139 ° C;

1-methyl-5-3- (3,5-di-tert.butyl-4-10 hydroxyphenyl) thiopropyl thio-1,2,3,4-tetrazole, light yellow needles (methanol-water), tons mp, 76-77 ° C; . . Methyl-5- 3- (5-amino-1,3,4-thiadiazol-2-yl) thiopropyl thio-1,2,3,4-tetrazol, colorless prisms (ethanol), m.p. 120.5-122 0;

1-methyl-5-z- (5-methyl-1,3,4-oxydiazol-2-yl) thiopropyl thio-1,2,3,4-tetrazole, colorless liquid, f 1.5644;

1-methyl-5- 3- (p-naphthyl) thiopropyl thio-1,2,3,4-tetrazole, colorless needles (ethanol), so pl. 56-58 ° C;

1-methyl-5-Z- (2-quinolyl) thiopropyl thio-1,2,3,4-tetrazole, light yellow needles (methanol), mp. 87-89 C;

1-metsh1-5- (4-phenylthiobutyl) thio- -1,2,3,4-tetrazole, colorless prisms (ethanol), mp, 51,

1-methyl-5- 4- (2-carboxyphenyl) thiobutyl thio-1,2,3,4-tetrazole, light yellow prisms (ethanol), mp. 143.6- -144,

1-methyl-5- 4- (2-methylphenyl) thiobutyl thio-1,2,3,4-tet1 azole, colorless liquid ,. 3 1.5786;

1-methyl-3-14- (2-aminophenyl) thiobutyl thio-1,2,3,4-tetrazole, yellow liquid, n 1.5961;

1-methyl-5-4- (4-chlorophenyl) thiobutyl thio-1,2,3,4-tetrazole, colorless liquid, Pr 1.5971; j 1-methyl-5- 3- (2-furylmethyl) thio-thio-1,2,3,4-tetrazole, brown,

16.S

thirty

35

40

) Neva liquid, p

1.5641;

1-methyl-5 (3-benzylthiopropyl) thio- -1,2,3,4-tetrazole, colorless liquid. 1.5856;

1-methyl-5- 3- (4-chloro-rbenzyl) thiopropyl thio-1,2,3, .4-tetrazole, colorless liquid, .. According to 1.5858;

1-methyl-5-z- (4,5-dimethyl-1,2,4-triazol-3-yl) thiopropyl thio-1,2,3,4-tetrazole, colorless prisms (ethanol-hexane), m.p. 74-77 C;

1-methyl-5-СЗ- (quinazolin-4-one-2-yl) thioprogase, - 2,3,4-tetrazole, colorless flakes (ethanol-hexane), so pl. 132.5-134,

1-methyl-5- 4 (3N, 4H-1,3,4-free-triazepin-5-one-2-yl) -thiobutyl thio- -1,2,3,4-tetrazole, colorless prisms, m.p. C (butanol);

1 g methyl-5- (3-ethylthiopropyl) thio- -1,2,3,4-tetrazole, colorless seat, front “1,5385s

 1-methyl-5-SZ-n butylthioprp1)

thio-1,2,3.4-tetrazole, yellow liquid, p - 1.5192;

1-metshg-5- (3-cyclopentylthiopropyl) -thio-1,2,3,4-tetrazole, light yellow liquid, П, "1.5469;

1-methylg-5-3- (2-pyridylmethyl) thiopropyl thio-J 2,3,4 tetrazole, brown liquid; 1.5820;

1-metsh1-5-z- (4-methyl-2-thiazolSH1) thiopropyl thio-1,2,3,4-tetrazole, colorless liquid, p "1.5919

1-methyl-5- 3-4-pyridyl) thiopropyl-thio-1,2,3,4-tetrazole, a lighter yellow liquid, Pr 1.6017;

1-methyl-5-Cz- (5-nitro-2-pyridyl) tyrosine-1,2,3,4-tetrazole. Light brown liquid, "1.6289;

1-metSH1-5-Z- (2-amino-4-methyl 6-chsh imidyl) thiopropyl thio-1,2,3,4-

tetrazole, colorless crystalline powder (methanol), so pl. 119-120 ° C;

I-methyl-5- 2- (2-furylmethyl) thioethy; thio-1,2,3,4-tetrazole, light

m

Brown, HJ,

1.57P;

1-methyl-5- {3- (2-aminot4-ggiazolsh1). methyl thiopropyl | thio-1,2,3,4-tetrazole, yellow prisms (methanol-water), mp, 117-117,

1 Cyclohexyl-5-3- (1-cyclohexyl-1,2,3,4-tetrazo-1-5-yl) thioprosh thio-1,2,3,4-tetrazole, light yellow granules (ether-ztaiol ), so pl. 88.5- .89.

1-meTSh1-5- 3- (1-phenyl-1,2,3,4-tetrazol-5-ip) thiopropyl thio-1,2,3,4-megetrazole, colorless prisms (ethanol jmrpoHH) mp . 89-90.5 C;

1 -metx-1-5- 5- (1 -methyl-1,2,3,4-β-tetrazol-5-yl) thiopentyl thio-1,2,3,4-tetrazole, colorless prisms (zethanol) T | PL . 64-65 ° C;

1-methyl-5- 6- (1-methyl-1,2,4,3-

tetrazo t5-yl) thiohexyl thio-1,2,3,4-tetrazole, colorless prisms (acetone) so pl. 91-93.5 0;

1-methyl-5- 2-methyl-3- (1-methyl--1,2,3,4 tetrazolt5-yl) thiopropyl thio -1,2,3,4-tetrazole, colorless prisms (ethanol), t. square 87-89.5 ° 0;

1-metsh1-5-Z-methyl-3- (1-methyl--1,2,3,4-tetrazolg-5-yl) thioprothio thio -1,2,3,4-tetrazole, colorless needles (ethanol ), so pl. 68.5-70,

1-methyl-5- 2-methyl Z- (2-pyridyl) thiopropyl thio-1,2,3,4-tetrazole, light yellow liquid, n 1.5936;

I-metesh-5-4- (4-methoxyphenyl) thio-butyl thio-1,2,3,4 g tetrazole, colorless liquid;

 NMR (90 MHz, CDOK), S: 1.50-2.20 (4H, cartoon); 2.83 (2H, triplet, J “6 Hz); 3.30 (2H, triplet, J "6 Hz); 3.77 (SA, singlet); 3.87 (SA, singlet); 6.82 (2H, doublet J - 9 Hz); 7.32 (2H, doublet, J - 9 Hz).

Example 50. 1-Methyl-5-mercapto-I, 2,3,4-tetrazrl (4.6 g) and 1,3-dibromopropane (4 g) are dissolved in acetone (50 ml). Potassium carbonate (5.5 g) is added to the mixture and the mixture is heated to reflux for 3 hours. After distilling off the acetate, water is added to the residue, the precipitated crystals are filtered off and recrystallized from ethanol, to give 1-methyl -5-1.3- (1-methyl-1,2,3 i 4- -tetra azol-5-yl) thioprosh-thio-1,2,3,4-tetrazole (3.6 g) in the form of colorless prisms, t .: w1. 141.5-143 5 S.

Calculated Z: O 30.87; And 4.44; N41.14

Found,%: O 30.68; And 4.37;

N41.32.

Example 51. In Example 50, the following compounds were prepared:

1-metshg-5- 4- (1-metSH1-1,2,3,4-β-tetrazol-5-yl) thiobutyl thio-1,2,3,4-tetrazole, colorless needles (ethanol), m.p. 122-

1-phenyl-5- 3 - (} - phenyl-1 2,3,4-β-tetrazol-5-yl) thiopropyl thio-1,2,3,4-tetrazole, colorless needle-like crystals (methanol-chloroform ), so pl. 81-82 0;

1-phenyl-5- 4- (1-phenyl-1,2,3,4 - -: tetrazol-5-yl) thiobutyl thio-1,2,3,4-tetrazol, colorless needles (ethanol-chloroform ), mp, 127-128,

1-cyclohex sil-5 3- (1-cyclohex forces -1,2,3,4-H etrazol-5-yl) thiopropyl-1,2,3,4-tetrazole, light yellow granules (ester ethanol), mp, 88.5-89.5 C;

1-methyl-5- 5- (1-methyl-1,2,3,4-heterzol-5-Sh1) thiopentyl} thio-1,2,3,4-tetrazol, colorless prisms (ethanol) t. square 64-65 ° C;

1-metip-5-b- (1-metSH1-; 1 у2,3,4-tetrazol-5-yl) thiohexyl thio-1 j 2,3,4-tetrazole, colorless prisms (acetone) t.pl . ai-93 C:

. 1methyl-5- 2-metsh-3- (1-methyl solution of 5-nitro-2-chloropyridine (1.9 g) in acetone (20 ml) while cooling with ice. After the addition, the mixture is stirred at room temperature - 5 times for 3 hours Acetone is distilled off, water is added to the residue. The mixture is extracted with e (rum, the ether solution is taken up with a dilute aqueous solution of sodium hydroxide, saturated with an aqueous solution of sodium chloride, and dried with sodium sulfate. After distillation, the residue is purified by chromatography (Kiesel gel 60, solvent : n-hexane-eff | p 4: 1), get

, 2,3,4-tetrazol-5-yl) thiopropshthio-15 1-methyl-5 - (: 3 g of (5-nitro-2-pyridal) thio- -1,2,3,4-tetrazole ,. colorless prisms propyl thio-I, 2,3,4-tetrazole (1.4 g) (ethanol), mp, 5 ° C; light brown liquid, n 1-methyl-5- 3-methyl-3- (1-methyl- -1,2,3,4-: tetraZO5-yl) thiopropsht tch -1,2,3,4-tetrazol, colorless needle-like crystals (ethanol), so pl. 68,5 -,

Found,%: C 38.46; H 3.68; N 27.01

Example 55. In Example 54, the following compounds were prepared:

 1-methyl-5-Hz- (2-pyridyl) thiopropyl-Thio-1, 2,3,4-tetrazole, a light yellow liquid, n 1.6022;

1.-notcht5-4- (2-pyridyl) thiobutyl thio-I, 2,3 4-tetrazole, light yellow prisms, so pl. 49-51, (ethanol-water);

1-methyl-5- 5- (2-pyridyl) thiopentylTo thio-1,2,3,4-tetrazole, colorless liquid, njj 1,5853;

"1,6289.

Calculated,% C 38.46; H 3.85; N 26.92

25

thirty

70 ,.

Example 52.. l-Methl-5- (3-mercaptopropropyl) thio-l, 2,3,4-tetrazole (1.9 g) was dissolved in 1N aqueous sodium hydroxide solution (30 ml) and a solution of cyclohexyl bromide (2 g) in acetone. (20 ml) with stirring and cooling with ice. After the addition, the mixture is stirred at room temperature for 3 hours. The acetone is distilled off, water is added to the residue and the mixture is extracted with ether. The ether solution is washed with a dilute aqueous solution of sodium hydroxide and with a saturated aqueous solution of sodium chloride, and dried with sodium sulfate. After the ether has been distilled off, the residue is purified by chromatography (Kieselgel 60, zluent: n-hexane-ether 4: 1). Get 1-methyl-5- - (3-cyclohexy silthiopropyl) thio-1,2,3,4-tetrazole (1.5 g), colorless liquid, nL

C (OH, 1 NjS2

35

1-methyl-5- b- (2-pyridyl) thiohexyl thio-1,2,3,4-tetrazole, colorless prisms, m.p. 58-60 s (ethanol);

1-methyl-5-3- (3-hydroxy-2-pyridyl) thiopropyl thio-1,2,3,4-tetrazole, light yellow granules, mp. 87.5-88.5 Cj

1.5433.

%: C 48.53} H

7.35;

Calculated M 20,59

Found,%: C 48.40; H 7.58; N 20.41.

Example 53. In Example 52, 1-cyclohexyl-5- (3-methyl-tyrode) thio-1,2,3,4-tetrazole is obtained, colorless liquid, p 1.5433,

Example 54. 1-Methyl-5- (3- -mercaptothiopropyl) thio-1,2,3,4-tetrazole (1.9 g) is dissolved in 1 and. an aqueous solution of sodium hydroxide (30 ml) and added dropwise there

1-methyl-3- (4-methyl-2-pyrimidyl) thiopropyl thio-1,2,3,4-tetrazole, colorless liquid, Hjf 1.5853;

1-methyl- 5- 3- (2-benzimidazolyl) 5 thiopropyl thio-1,2,3,4-tetrazole, colorless needles (ethanol) so pl. 137-139 ° C;

J-methyl-5-z- (3,5-di-tert-butyl-4g-hydroxyphenyl) thioprothia thio-1,2,3,4-tetrazol, light yellow needles (methanol-water), t .pl. 76-77 ° C;

1 -Metshg-5-z- (5-amino-1,3,4-thiad and azol-2-yl) thiopropyl thio-1,2,3,4-tet-, razol, colorless prisms (ethanol) m.p. 120.5-122 ° C;

1-Mefil-5- 3- (5-methyl-J, 3.4-0x-diazol-2-yl) thiopropyl thio-1,2,3,4 "1,6289.

Calculated,% C 38.46; H 3.85; N 26.92

Found,%: 7.01

C (OH, 1 NjS2

1-methyl-5- 5- (2-pyridyl) thiopentylTo thio-1,2,3,4-tetrazole, colorless liquid, njj 1,5853;

five

1-methyl-5- b- (2-pyridyl) thiohexyl thio-1,2,3,4-tetrazole, colorless prisms, m.p. 58-60 s (ethanol);

1-methyl-5-3- (3-hydroxy-2-pyridyl) thiopropyl thio-1,2,3,4-tetrazole, light yellow granules, mp. 87.5-88.5 Cj

1-methyl-3- (4-methyl-2-pyrimidyl) thiopropyl thio-1,2,3,4-tetrazole, colorless liquid, Hjf 1.5853;

1-methyl-5- 3- (2-benzimidazolyl) thiopropyl thio-1,2,3,4-tetrazole, colorless needles (ethanol) so pl. 137-139 ° C;

J-methyl-5-z- (3,5-di-tert-butyl-4g-hydroxyphenyl) thioprothia thio-1,2,3,4-tetrazol, light yellow needles (methanol-water), t .pl. 76-77 ° C;

1 -Metshg-5-z- (5-amino-1,3,4-thiad and azol-2-yl) thiopropyl thio-1,2,3,4-tet-, rasol, colorless prisms (ethanol), m.p. 120.5-122 ° C;

1-Mefil-5- 3- (5-methyl-J, 3,4-0x-diazol-2-yl) thiopropyl thio-1,2,3,4-tetrazole, colorless liquid, 1.5644;

1-methyl-5- 3 (p-naphthyl) thiopropyl thio-1,2,3,4-tetrazole, colorless crystals (ethanol), T.PL. Zb-ZV S;

1-methyl-5-3- (2-quinol yl) thiopropyl) thio-1,2,3,4-tetrazole, pale yellow crystals (methanol), so pl. 87-89 ° C;

1-metshg-5- (4-fensh1thiobutyl) thio- -1,2,3,4-hetrazole, colorless prisms (ethanol), so pl. 51.5-53 ° C;

1-methyl-5- 4- (2-carboxyphenyl) thiobutyl thio-1,2,3,4-tetrazole, pale yellow prisms (ethanol), mp, 143.5-144.5 ° C}

1-methyl-5- 4- (2-methylphenyl) thiob-,: thyl-thio-1,2,3,4-tetrazole, colorless liquid, n - 1.5786;

1-methyl-5- 4- (2-aminophenyl) thiobyte

l-methyl-5- 3- (4-methyl-2-thiazolyl) thiopropyl thio-1,2,3,4-tetrazole, colorless liquid, h J,

1.5919;

to

IS

1-methyl-5- | 3- (4-pyridyl) thiopropyl thio-1,2,3,4-tetrazole, pale yellow liquid, pv. 1.6017;

1-methyl-5-3- (2-amino-4-methyl-6-pyrimidyl) thiopropyl-thio-1,2,3,4-tetrazol is a colorless crystalline powder (methanol), m.p. 119-120 ° C;

1-metsh-1-5- 2- (2-furSh1methyl) thioethyla thio-1,2,3,4-tetrazole, pale brown liquid, PP 1.5711;

1-methyl-5-Z- (2-amino-4-thiazolyl) methylthiopropyl thio-1,2,3,4-tetrazole, yellow prisms (methanol-water), so pl. 117-118,

1-cyclohexyl-5-z- (1-cyclohexylthio-thio-1, 2,3,4-tetrazole, yellow liquid- 20-1,2,3,4-tetrazol-5-yl) thiosthyde, Pr 1.5961 -1,2,3,4-tetrazole, pale yellow

1-methyl-5-4- (4-chlorophenyl) thiobutyl granules (ether-ethanol), mp. 88,5thio-1, 2,3,4-tetrazole, colorless liquid-89,

g9

bone, nj,

1.5971;

1-metsh1-5- 3- (1-fensh1-1,2,3,41-methyl 5- 3-: (2-furylmethyl) thiopro-25-tetrazol-5-yl) thiopropyl thio-1,2,3 , 4-, 2,3, A-tetrazole, brown-tetrazole, colorless prisms (ethanol fluid, pd 1.5641; ligroin), so pl. 89-90,5 C ;,

1-methyl-5- 5- (1-methyl-1,2,3,4-tet-: rasol-5-yl) thiopentyl thio-1,2,3,4-tet-30 razol, colorless priest l ( ethanol), so pl. 64-65 ° C;

1-methyl-5-Sat- (1-methyl-1,2,3,41-methyl-5- (3-benzylthiopropyl) thio-.-1,2,3,4-tetrazole, colorless liquid, n "5 1.5856;

1-methyl-5-З- (4-chloroben zyl) thiopropyl thio-1,2,3,4-tetrazole, colorless liquid. n-Q .. 1.5853;

1-methyl-5- 3- (4,5-dime-1,2,4-triazol-3-yl) thiopropyl thio-1,2,3,4-35-tetrazole, colorless prisms (ethanol- hexane), mp, 74-77 ° C;

1-methyl-5-H- (quinazolin-4-one-2-yl thiopropyl thio-1,2,3,4-tetrazole, colorless flakes (ethanol-hexane), mp 132.5-134,

40

: tet

Razol-5-ylj thiohexyl thio-1,2,3,4-tetrazole, colorless prisms (acetone), so pl. 91-93.5 ° C; 1-methyl-5- 2-ethyl-3- (1-methyl--1,2,3,4-tetrazol-5-yl) thiopropyl thio- -1,2,3,4-tetrazole, colorless prisms (ethanol ), so pl. 87-89.5 ° C; 1-methyl-5- 3-methyl-3- (1-methyl--1,2,3,4-tetrazol-5 yl) thiopropyl thio-1,2,3,4-tetrazole, colorless needles (ethanol), m.p. 68.5-70.5 C; 1-methyl-5- 2-methyl-3- (2-pyridi 0

1-methyl-5-4- (3N, 4H-1,3,4-benzo-tripyasin-5-one-2-pcs) thiobutyl thio- -1,2,3,4-tetrazole, colorless prisms, mp . 94-95 ° C (methanol);

1-methyl-5- (3-ethylthiopropyl) thio--1,2,3,4-tetrazole, colorless liquid, p 1.5385;

1-methyl-5- (3-n-butylthiopropyl) thio -1, 2,3,4-tetrazole, yellow liquid.

P

29

 1.5192; 1-methyl-5- (3-cyclone-thiopropyl

thio-1,2,3,4-tetrazole, a pale yellow liquid, p 1.5469;

1-methyl-5-3- (2-pyridylmethyl thiopropyl thio-1, 2,3,4-tetrazole, brown liquid, h 1.5820;

l-methyl-5- 3- (4-methyl-2-thiazolyl) thiopropyl thio-1,2,3,4-tetrazole, colorless liquid, h J,

1.5919;

1-methyl-5- | 3- (4-pyridyl) thiopropyl thio-1,2,3,4-tetrazole, pale yellow liquid, pv. 1.6017;

1-methyl-5-3- (2-amino-4-methyl-6-pyrimidyl) thiopropyl-thio-1,2,3,4-tetrazol is a colorless crystalline powder (methanol), m.p. 119-120 ° C;

1-metsh-1-5- 2- (2-furSh1methyl) thioethyla thio-1,2,3,4-tetrazole, pale brown liquid, PP 1.5711;

1-methyl-5-Z- (2-amino-4-thiazolyl) methylthiopropyl thio-1,2,3,4-tetrazole, yellow prisms (methanol-water), so pl. 117-118,

1-cyclohexyl-5-z- (1-cyclohexyl-1, 2,3,4-tetrazol-5-yl) thio-thio5 C;

1-metsh1-5- 3- (1-fensh1-1,2,3,4trazol-5-yl) thiopropyl thio-1,2,3 trazol, colorless prisms (ethane

1-methyl-5-Sat- (1-methyl- 1,2,3,4

: tet

Razol-5-ylj thiohexyl thio-1,2,3,4-tetrazole, colorless prisms (acetone), so pl. 91-93.5 ° C; 1-methyl-5- 2-ethyl-3- (1-methyl--1,2,3,4-tetrazol-5-yl) thiopropyl thio- -1,2,3,4-tetrazole, colorless prisms (ethanol ), so pl. 87-89.5 ° C; 1-methyl-5- 3-methyl-3- (1-methyl--1,2,3,4-tetrazol-5 yl) thiopropyl thio-1,2,3,4-tetrazole, colorless needles (ethanol), m.p. 68.5-70.5 C; 1-methyl-5- 2-methyl-3- (2-pyridi 0

thiopropyl thio-1,2,3,4-tetraz6l, pale yellow liquid, front 1.5936;

1-methyl-5- 4- (4-methoxyphenyl) thiobutyl thio-1,2,3,4-tetrazole, colorless liquid, NMR (90 MHz, SOSC), 8:

1.50-2.20 (4H, m) {2.83 (2H, t J 6 Hz); 3.30 (2H, t J - 6 HZ); 3.77 (3N, S); 3.87 (3H; S); (2H, d, J 9 Hz); 7.32 (2H, d, J 5-

55

PRI me R 55.

A. 2-Mercaptopyridine (1.3 g) and 1-methyl-5- (4-bromobutyl) thio-1,2,3,4-tetrazole (2 g) are dissolved in acetone

(50 ml), Potassium carbonate (1, A g) is added to the mixture and the mixture is boiled for 2 hours. After the acetone is distilled off, water is added to the residue, the precipitated crystals are filtered and recrystallized from ethanol-water, to give 1-methyl-5- 4- (2-pyridyl) thiobic; Thio-l, 2,3,4-tetrazole (1.7 g) as pale yellow prisms, mp. 49-51.5 C,

Calculated,% С, 46.98; H 5.34; N 24.91

- C,; H ,, N, S

Found,%: C 46.47; H 5.27;

N 24.94

B. Mercaptobenzene (1.3 g) and 5- - (3-bromopropyl) -thio-1,2,3,4-tetrazole (1.8 g) is dissolved in acetone (50 ml) and carbonate is added to the solution. ka LIA (1.4 g). The mixture is refluxed for 2 hours, the acetone is evaporated, water is added to the residue, and the mixture is extracted with chloroform. The chloroform layer is washed with a 5% solution of sodium hydroxide, with a saturated aqueous solution of sodium chloride and dried with magnesium sulfate. After distilling off the chloroform, the residue is purified on a chromatographic column {Wacogel, a zliruyushchy agent — chloroform) to obtain 5- - (3-phenylthiopropyl) thio-1, 2,3,4-tetrazole (1.5 g) as a colorless liquid

Calculated,%: C, 47.59; H 4.79; N 22.20

C (O

Found,%: C 47.62; H 4.80;

N 22.15

Example. 56, In Example 55A, the following compounds were obtained:

1-methyl-5- (3-cyclohexylthiopropyl thio-1,2,3,4-tetrazole, colorless liquid, nj, 1.5433;

1-metshg-5-z- (2-pyridyl) thiopropyl thio-1,2,3,4-tetrazole, pale yellow liquid, Pr 1.6022;

1-cyclohexyl-5- (3-ттш1-thiopropyl) thio-1,2,3,4-tetrazole, colorless liquid, y 1.5433;

 1-methyl-5-3- (I-methyl-1,2,3,4t-tetrazol-5-yl) thiopropyl thio-1,2,3,4 -herazole, colorless prisms (ethanol t, sh1. 141, 5-143,

1-methyl-5- 4- (1-methyl-1,2,3,4-tet-razol-5-yl) thio-butyl} thio-1,2,3,4-tet-

, Yu

15

20 25 to 35

0

five

five

Razol, colorless crystals (ethanol), T, fm. 122-123 C;

1-phenes 1-5-4- (1-phenyl-1,2,3,4-tetrazol-5-yl) thiobutyl thio-1,2,3,4-tetrazole, colorless needles (ethanol-chloroform), mp. 127-128,

1-methyl-5- 3 - (- cyclohexyl-1,2,3, - 4-tetrazol-5-yl) thiopropyl thio-1,2,3,4-tetrazole, pale yellow liquid.

P 1,5653:

1-Fensch1-5-3- (1-phenyl-1, 2,3,4-tetrazol-5-yl) thiopropyl thio-1,2,3,4-tetrazole, colorless needles (methanol-chloroform), mp: 81-82 ° C;

1-methyl-2-3- (1-methylimide azole-2 g -L) thio propyl thio-1,2,3,4-et p azole, colorless needles (ester), mp, 59.5- 60.5 ° C;

1-methyl-5- (3-phenylthiopropyl) thio--1, 2,3,4-tetrazole, colorless liquid, p - 1.6008;

1-methyl-5- 2- (2-pyridyl) thiosyl thio-1,2,3,4-tetrazole, colorless prisms, mp, 77-79, (ethanol),

1-methyl-5-f 5- (2-pyr1adyl) thiopentyl thio-1,2,3,4-tetrazole, a colorless liquid, According to 1,5853;

1-TI71-5- 6- (2-pyridyl) thio g ecyl thio-1,2,3,4-tetrazole, colorless prisms, so pl. 58-60 ° C (ethanol);

1-methyl-5-z- (3-hydroxy-2-pyridyl) thiopropyl thio-1,2,3,4-tetrazole, pale yellow granules, mp, 87.5-88.5 C (hexane ethyl acetate);

1-methyl 5-z- (4-methyl-2-pyridsh1) thiopropyl thio-1,2,3,4-tetrazole, colorless liquid, 1.5853;

1-methyl-2- 4- (1-metsh1-1,2,3,4-tetrazol-5-sh1) tyobutyl isothiourea hydrobromide, white crystalline powder (acetone), t, mp, 116.5-118 s (dec);

1-methyl-5-z- (2-benzimidazolyl) thiopropyl thio-1,2,3,4-tetrazole, colorless needles (ethanol), t, pl. 137-139 C;

1-methyl-5- 3- (3,5-di-tert-butyl-4-0xyphenyl) thiopropyl} thio-1,2,3,4-tetrazol, pale yellow crystals (methanol-water), t , pl, 7b-77 ° C;

1-metshg-5-z- (5-amino-1,3,4-thiadiazol-2-yl) thiopropyl thio-1,2,3,4-tetrazol, colorless prisms (ethanol); t, pl, 120.5-122 ° C;

1-methyl-5-z- (5-ythyl-1,3,4} -oxadiazol-2-yl) thiopropyl thio- -1,2,3,4-tetrazole, colorless liquid, 1.5644;

1-methyl-5- 3- (|} -naphthyl) thiopropyl thio-1,2,3,4-tetrazole, colorless needles (ethanol), so pl. .WITH;

 1-methyl-5- 3- (2-quinolyl) thiopropyl, 2,3,4-tetrazole, pale yellow needles (methanol), so pl. 87-89 C;

1-methyl-5- (4-phenylthiobutyl) thio- -1,2,3,4-tetrazole, colorless prisms (ethanol), so pl. 51,

1-methyl-5- 4- (2-carboxyphenyl) thiobutyl thio-1,2,3,4-tetrazole, pale yellow prisms (ethanol), mp. 143.5-144.5 ° C;

1-metsh1-5-4- (2-methylphenyl) thiobutyl thio-1,2,3,4-tetrazole, colorless liquid, p 1,5786;

1-methyl-5- 4- (2-aminophenyl) thio-butyl thio-1,2,3,4-tetrazole, yellow liquid, Pr 1.5961;

1-methyl-5- 4- (4-chlorophenyl) thiobutylSthio-1,2,3,4-tetrazole, colorless liquid, PD, 1.5971;

1-methyl-5-3- (2-furylmeth 1) thio-propyl thio-1,2,3,4-tetrazole, brown liquid, n 1.5641;

1-methyl-5- (3-benzylthiopropyl) thio- -1,2,3,4-tetrazole, colorless liquid, Pd 1.5856;

1-methyl-5- 3- (4-chlorobenzyl) thiopropyl thio-1,2,3,4-tetrazole, colorless liquid, PV 1.5858;

1-methyl 75- 3- (4,5-dimethyl-1,2,4-triazol-3-yl) thiopropyl thio-1,2,3,4-tetrazole, colorless prisms (zethanol hexa), m.p. . 74-77 ° C;

1-methyl-5-З- (quinazolin-4-one-2-III thiopropyl thio-1,2,3,4-tetrazole, colorless flakes (ethanol-hexane), mp 132.5-134 ,.

1-methyl-5- 4- (3N, 4H-1,3,4-benzotriazepuping-5-one) thiobutyl thio-1,2,3,4-tetrazole, colorless prisms, mp. 94-95 ° C (methanol) ;.

1-methyl-5- (3-ethylthiopropyl) thio- -1,2,3,4-tetrazole, colorless liquid, Pd 1.5385;

1-methyl-5- (3-n-butylthiopropyl) thio -1,2,3,4-tetrazole, yellow liquid, n 1.5192;

1-methyl-5- (3-cyclopentyl thiopropip thio-1,2,3,4-tetrazole, pale yellow liquid, p 1.5469;

1-methyl-5-OZ- (2-pyridylmethyl) thiopropyl thio-1,2,3,4-tetrazole, brown

va liquid, p

1.5820;

1-methyl-5- 3- (4-methyl-2-thiazolyl) thiopropyl thio-, 2,3,4-tetrazole, colorless liquid, Pd "1.5919;

1g; methyl 5-З- (4-pyridyl) thiopropyl | thio-1,2,3,4-tetrazral, pale yellow liquid, 1.6017;

1-methyl-5-z- (2-amino-4-methyl-6-pyrimidyl) thiopropyl thio-1,2,3,4-tetrazole, colorless crystalline powder (methanol) I m.p. 119-120 C;

1-methyl-5- 2- (2-phyrylmethyl-thio-ethyl-l-thio-l, 2,3,4-tetrazole, pale yellow liquid, p 1.5711;

1-methyl-5- {3- (2-amino-4-thiazolyl) methylT-thiopropyl thio-1,2,3,4-tetrazole yellow prisms (methanol-water), m.p. 117-118.5 ° C;

1-cyclohexyl-5-z- (1-cyclohexyl-1,2,3,4-tetrazol-5-yl) thiopram evol thio-1,2,3,4-tetra azole, pale yellow granules (ester-ethanol) mp. 85.5-89.5 C

1-methyl-5-z- (1-phenyl-1,2,3,4-β-tetrazol-5-yl) thiopropyl thio-1,2,3,4-tetrazole, colorless prisms (zthanally ligroin), m.p. 89-90.5 ° C;

1-methyl-5- 5- (1-methyl-1,2,3,4-tetrazol-5-yl) thiopent-1 thio-1,2,3,4-tetrazol, colorless prisms (ethanol) t. square 64-65 ° C;

1-methyl-5-z- (5-nitro-2-pyridsh1) thiopropyl thio-1,2,3,4-tetrazole, pale yellow liquid, HD

1.6228;

I

1-methyl-5- 6- (1-methyl-1, 2,3 4-tetrazol-5-yl) thiohexe thio-1,2,3,4-tetrazole, colorless prisms (acetone), so pl. 91-93.5 ° C .;

1-methyl-5- 2-methyl-3- (1-methyl--1,2,3,4-tetrazol-5-yl) thioprothio-1,2,2,4-tetrazole, colorless prisms (ethanol ), so pl. 87-89.5 C;

1-metsh1-5-Z-methyl-3- (1-methyl--1,2,3,4-tetrazol-5-yl) thiopropyl thio-1,2,3,4-tetrazole, colorless needles (ethanol) m.p. 68 ,,

1-methyl-5- 2-methyl-3-2-pyridyl) thiopropyl thio-1,2,3,4-tetrazole, pale yellow liquid, n 1.5936;

1-methyl-5-4- {4-methoxyphenyl) butyl thio-1,2,3,4-tetrazole, colorless-on-liquid, NMR (90 MHz, CDCl,) 5 ;, ppm 1.50-2.20 (4H, t); 2.83 (2H, tJ 6 Hz); 3.30 (2H, t, J - 6 Hz); 3.77 (3N, S); 3.87 (3N, S); 6.82 (2H, d, J 9 Hz); 7.32 (2H, d, J 9 Hz).

EXAMPLE 57. 1-Uthyl-5- (4-chlorobutyl) thio-1,2,3,4-tetrazole (2.00 g) and 2-mercapto-3H, 4H-benzotriazepine 5-one (2.2 g) is dissolved

in methanol (50 ml), sodium hydroxide (4.8 g) is added to the solution and the mixture is refluxed for 2.5 h. The solvent is distilled off, water is added to the residue and the mixture is extracted with chloroform. Chloroform with aqueous pacTBQpoM sodium hydroxide and saturated sodium chloride solution, then dried with magnesium sulfate, Chloroform is distilled off, the residue is recrystallized from methanol, to obtain 1-methyl-5-4- (3N, 4R) -l, 3, 4-benzo-tripia-5-one 2-yl thiobutyl thio- -1,2,3,4-tetrazole (2.4 g) as colorless prisms, mp. 94-95 C.

Calculated,%: C 46.29; H 4.68; 27.0

SNNd NjQS

Found,%: C-46,14 ;, H 4.45; 26.89.

Example 58. In Example 57, the following compounds were prepared:

1-methyl-5- (3-cyclohexylthiopropyl) thio-1,2,3,4-tetrazole, colorless liquid, p 1.5433;

I is methyl-4-W- (2-pyridyl) tyropropyl thio-1,2,3,4-tetrazole, pale yellow liquid, Ai 1.6022;

1-cyclohex SSh1-5- (Zz tiltiopropil) thio-1,2,3,4-tetrazole, colorless liquid, p 1.5433;

1-methyl 5-3- (1-methyl-1,2,3,4-β-tetrazol-5-yl) thioprosh

-1,2,3,4-tetrazole, colorless lrizma (ethanol), mp, 141-, 5-143,

1-methyl-5- 4- (1-methyl-1,2,3,4-α-tetra azol-5-yl) thiobutyl thio-1,2,3,4-β-tetrazol, colorless needles (ethanol, mp 122-123 ° C;

1-phenyl-5- 4- (1-phenyl-1,2,3,4-tetrazol-5-yl) thiobutyl thio-1,2,3,4-tetrazole, colorless needles (ethynol chloroform) m.p. 127-128,

. 1gmethyl-5- 3- (1-cyclohexyl- -1,2,3,4-tetrazol-5-Sh1 thioprothio thio -1,2,3,4-tetrazole, pale yellow v liquid, Pu. 1.5653;

-phenyl-5- 3- (1-fenshg-1,2,3,4-tetrazol-5-yl) thiopropyl thio- -1,2,3,4-tetrazole, colorless needles (methanol-chloroform), t .pl. 81-82 0;

j

u 15 20

0

five

1-methyl-2- 3- (1-methylimidaz6l-2- -yl) thiopropyl, 2,3,4-tetrazole, bez. crystals (ether), mp 59.5-.60,. . .

1-methyl-5- (2-Fensch-Thiopropyl) thio- -1,2,3,4-tetrazole, colorless liquid 1,6008;

1-methyl-5- 2- (2-pyridyl) thioethyl thio-1,2,3,4-tetrazole, colorless prisms, m.p. (ethanol);

1-methyl-5- 4- (2-pyridyl) thiobutyl thio-1,2,3,4-tetrazole, pale yellow prisms, so pl. 49-51, (ethanol-water);

1-methyl-5- 5- (2-pyridyl) thiopentyl thio-1,2,3,4-tetrazole, colorless liquid, Pd 1,5853;

1-methylg5-b- (2-pyridyl) thio gexyl thio-1,2,3,4-tetrazole, colorless prisms, mp. 58-60 with (ethanol).

1-methyl-5-Z- (3-hydroxy-2-pyridyl) thiopropyl thio-1,2,3,4-tetrazole, pale yellow granules, mp. 87.5-88,

1-methyl-5- 3- (4-methyl-2-pyrimidyl) thiopropyl thio-1,2,3,4-tetrazole, bes. color, 1.5853;

1-methyl-5-W- (2-benzimidazolsh1) thiopropyl thio-1,2,3,4-tetrazole, colorless needles (ethanol), so pl. 137- 139 ° C;

1-methyl-5-З- (3,5-di-tre, butyl-4-oxyfene) thiopropyl-thio-1,2,3,4-tetrazol, pale yellow needles (methanol ode) m.p. 76-77 C;

1-methyl-5-3- (5-amino-1,3,4-thiadiazol-2-yl) thiopropyl thio-1,2,3,4-tetrazole, colorless prisms (ethanol), m.p. 120.5-122 ° C;

1-methyl-5-3- (5-methyl-1,3,4-oxydiazol-2-yl) thiopropyl thio-1,2,3,4-tetrazole, colorless liquid.

five

nf 1.5644;

1-methyl-5-Z- (p-naphthyl) thiopropyl thio-1,2,3,4-tetrazole, colorless needles (ethanol), so pl. 56-58 C;

1-methyl-5-Z- (2-quinolyl) thiopropyl thio-1,2,3,4-tetrazole, pale yellow needles (methanol), so pl. 87-89 C;

1-methyl-5- (4-phenyl thiobutnl) thio--1,2,3,4-tetrazole, colorless prisms (ethanol), so pl. 51.5-53 ° C;

1-methyl-5- 4- (2-carboxyphenyl) thiobutyl thio-1,2,3,4-tetrazole, pale yellow prism (ethanol), m.p. 143.5-144,

1-methyl-5-C4- (2-methylphenyl) thiobutyl thio-1, 2,3,4-tetrazole, colorless liquid, front t 1,5786;

1-meth; d-5- A- (2-aminophenyl) thiobutyl thio-1,2,3,4-terazol, yellow liquid, ni 1.5961;

I-methyl-5- 4- (4-chlorophenyl) thiobuty, thio-1,2,3,4-tetrazole, colorless liquid, Pp 1.5971;

1-methyl-5-3- (2-furylmethyl) thiopropyl thio-1,2,3,4-tetrazole, brown liquid, Pd 1.5641;

„1-methyl-5- (3-benyltiopropyl) thio-I, 2,3,4-tetrazole, colorless liquid, Djj 1,5856;

1-methyl-5-Z- (4-chlorobenzyl) thiopropyl thio-1,2,3,4-tetrazole, colorless to liquid, 1.5858;

1-methyl-5-Z- (4,5-dimethyl-1,2,4-triazol-3-yl) thiopropyl thio-1,2,3,4-tetrazol, colorless prisms (ethanol, hexane), t .pl. 74-77 C;

1 metip-5-3- (hiiazolin-4-one-2-yl thiopropyl thio-1,2,3,4-tetrazole, colorless scales (ethanol-hexane), mp 132.5-134,

1-methyl-5- (3-e-tiltio propyl) tyr- -1,2,3,4-tetrazole, colorless liquid, 1.5395;

1-methyl-5- (3n-butylthiopropyl) thio -1,2,3,4-tetrazole, yellow liquid, 1.5192;

1-methyl-5- (3-cyclohexylthiopropyl thio-1,2,3,4-tetrazole, pale yellow liquid, .. nj) 1.5469;

1-methyl-5-z- (2-pyridylne-thyl) thiopropyl thio-1,2,3,4-tetrazole, brown liquid, HD 1.5820;

1-methylt5-z- (4-methyl-2-thiazolyl) thiopropyl thio-1,2,3,4-tetrazole, colorless liquid, p d 1.5919;

1-methyl-5-z- (4-pyridyl) thiopropyl thio-1,2,3,4-tetrazole, pale yellow liquid, Pd 1.6017;

1-methyl-5- 3- (5-nitro-2-pyridyl) thiopropyl thio-1,2,3,4-tetrazole, pale brown liquid, Pd - 1.6228;

1-methyl-5- 3- (2-amino-4-methyl-6-pyrimidyl) thiopropyl} thio-1,2,3,4-tetrazole, colorless crystalline powder (methanol), m.p. 119-120 ° C;

1-methyl-5- 2- (2-furyl-methyl) thioethyl thio-1,2,3,4-tetrazole, pale brown liquid, Pr 1.5711;

1-methyl-5- 3- 2-amino-4-tyazolyl) methyl} thiopropyl thio-1,2,3,4-tetrazole, yellow prisms (methanol-water), so pl. 117-118.5 ° C;

j

0

five

0

five

0

five

. 1 g-cyclohexyl-5- 3- (1 -cyclohexy -1,2,3,4-tetrazol-5-yl) thiopropyl thio -1,2,3,4-tetrazole, pale yellow granules (ether-atanol) m.p. 88.5-89,.

I-methyl-5-z- (1-phenyl 1,2,3, -tetrazol 5-yl) thiopropyl thio-1,2,3,4-tetrazole, colorless prisms of ethanol-ligroin), mp. 89-90,

1-metsh-5-5- (1-methyl-1,2,3,4-tetrazol-5-yl) thiopentyl, 2,3,4-tetrazole, colorless prisms () so pl. 64-65 seconds; . .......

1-methyl-5- 6- (1-methy -1,2,3,4-1. -Tetrazol-5-yl) thiohexip thio-1,2,3,4-tetrazole, colorless prisms (acetone) t .pl. 91-93,5 Cj

I-methyl-5- 2-methyl-3- (1-methyl--1,2,3,4-tetrazol-5-yl) thiopropyl thio-1,2,3,4-tetrazole, colorless prisms (ethanol) m.p. 87-89,

1-methyl-5-3-methyl-3- (1-methyl--1,2,3,4-tetrazol-5-yl) thiopropsh1) thio-1,2,3,4-tetrazole, colorless needles (zanol ), so pl. 68.5-70.5 ° C;

1-methyl-5- 2-methyl-g3- (2-pyridyl thiopropyl thio-1,2,3,4-tetrazole, pale yellow liquid, "1.5936;

1-methyl-5- 4- (4-methoxyphenyl) thio-butyl thio-1,2,3,4-tetrazole, colorless liquid, NMR (90 MHz, CDCI,),: 1.50-2.20 (4H, t); 2.83 (2H, t J 6 Hz); 3.30 (2H, t. J 6 Hz); 3.77 (3N, S); 3.87 (3N, S); 6.82 (2H, d, J - 9 Hz); 7.32 (2H, d, J 9 Hz).

Example 59. 1-Methyl-5- (3- -iodopropylthio) -1,2,3,4-tetrazole (2.8 g) and thiourea (0.8 g) are dissolved in ethanol (50 ml), cMjecb bale t under reflux for 2 h. After cooling, the precipitated crystals are filtered and dried, then dissolved in ethanol (50 ml). Cyclopetilbromide (1.3 g) and 10% aqueous sodium hydroxide solution (5 ml) are added to the mixture, the mixture is heated under reflux for 3 hours. Ethanol is distilled off and water is added to the residue. The mixture is extracted with chloroform. The extract is washed with a saturated aqueous solution of sodium chloride and dried over magnesium sulfate. After distilling off the chloroform, the residue is purified on a column (C-200 Wacogel, eluent; chloroform) to obtain 1-methyl-5- (3-cyclopentiptiopropyl) thio-1,2, 3,4-tetraeol (1.8 g) as pale - yellow liquid, p 1.5469; Calculated, 46.48; H 7.02; N 21.68

C ,,

Found,%: C 46.43; H 7,10} Ы 21,58.-

Example 60. In Example 59, the following compounds were prepared:

- methyl 5- (3-cyclohexylthiopr013 Thio-1,2, "3,4-tetrazole, colorless liquid, nj, 1.5433;

1-metsh1-5- 3- (2-pyridsh1) thiopropyl thio-1,2,3,4-tetrazole, pale yellow liquid J DD 4., 6022;

1-Cy lechexyl 5- (3-ethy-1-thiopropyl) thio-1,2,3,4-tetrazole, colorless liquid, n: “1.5433;

1 -Meth1-5-13- (I -methyl-: 1,2,3,4-tetrazol-5-yl) thiopropyl thio-1,2,3,4-tetrazol, colorless (ethanol m.p. 1.41.5-143.5 ° C;

1-methyl-5- 4- (1-methyl-1,2,3,4-tetrazol 5-yl) thiobutyl thio-1, 3,4-β-tetrazole, colorless needles (ethanol, mp. 122- 123 C;

1-phenyl-5- 4- (1-phenyl-1,2,3,4-β-tetrazol-5-yl) thiobutylSthio-1,2,3,4-tetrazole, colorless needles (ethanol, chloroform), t. square 127-128,5 Cj

2-metsshg-5-Z- (1-cyclohexyl-1,2, 3,4-tetrazol-5-yl) thiopropyl thio -}, 2,3,4-tetrazole, pale yellow

liquid, front 1,5653;

1-phenyl-5-З- (1-phenyl-1,2,3,4--tetrazolt5-yl) thiopropyl} thio-1.2,3,4 -tetrazol, colorless needles (methanol-chloroform), mp, 81-82 ° C;

-t4етt1-1- 3- (1-methylimidazol-2- - lithiopropyl3 thio-1,2,3,4-tetrazole, colorless needles (ether), t, pl. 59.5-60.5 C;

1-methyl-5-ch3-phenylthiopropyp) thio -1,2,3,4-tetrazole, colorless liquid, gp 1.6008.

Example 61, 1-Methyl-5- (3- -iodopropyl) thio 1,2,3,4-TeTpa3OJj (2.8 g) and S-methylthiourea (0.9 g) are dissolved in ethanol (50 ml) and the mixture is boiled reflux for 2 hours. After cooling, the precipitated crystals are filtered and dried. The crystals were dissolved in ethanol (50 ml) and then 2-pyridylmethyl chloride (1.4 g), a 10% aqueous solution was added.

sodium hydroxide (10 ml), and the mixture is heated under reflux for 1.5 hours. Ethanol is distilled off, water is added to the residue and the mixture is extracted with chloroform 1: 1. The extract is pierced with an aqueous solution of sodium chloride and dried over magnesium sulfate. After distilling off the chloroform, the residue is purified on a column (C-200 Wacogel, chloroAorg-methanol, J, 50: 1), to obtain 1-meth 1-5-3- (2-pyridylmethyl) thiopropyl thio-1,2,3,4 - tetrazol (2.7 g) as a brown liquid, p 1, 5820,

Calculated,%: C 46,95; H 5.37; N 24.89

With „H, jNjSj ,.

Found,%: C 46.81; H 5.41; N24.78.

Example 62. In Example 61, the following compounds are obtained:

.-methyl-5- 2- (2-pyridyl) thio ethyl thio-1,2,3i4-tetrazole, colorless prisms, mp 77-79.5 ° C (ethanol);

1-methyl-5- 4- (2-pyridyl) thiobutyl thio-1,2,3,4-tetrazole, pale yellow prisms, mp. 49-51, (ethanol-water);

1-methyl-5-5- (2-pyridyl) tyopentyl thio-1,2,3,4 t-tetrazole, colorless liquid, Pd “1.5853;

1-metsh1-5-5- (2-pyridyl) thiohexyl thio-1,2,3,4-tetrazole, colorless prisms, t, nn. 58-60 ° C (ethanol);

1-methyl-5- З- (3-0 xi-2-pyridyl) thiopropyl thio-1,2,3,4-tetrazral, but yellow granules, mp. 87.5-88, (hexane-ethyl acetate);

1-metshg-5-Z- (4-methyl-2-pyrimidyl) thiopropyl thio-1,2,3,4-tetrazole, colorless liquid, - 1.5853}

1-methyl-5-Z- (2-benzimidazolyl) thiopropyl thio-1,2,3,4-tetrazole, colorless needles (ethanol), mp, 137-,

1-methyl-5-З- (3,5-di-tert, butyl-4-o-c-sifesh) tyropyl thio-1,2,3,4-tetraeol, pale yellow needles (methanol-water), t .pl. 76-77 ° C;

1-methyl-5-3- (5-amino-1,3,4-thiadiazole 2-yl) thioproxy 1 thio-1,2,3,4-tetrazole, colorless prisms (ethanol), mp, 120 , 5-122 ° С;

I-methyl-5-З- (5-methyl-1,3,4-oxadiazol-2-yl) thioprosh1 thio-1,2,3,4-tetrazole, colorless liquid, n - 1.5644;

1-methyl-5- 3- (p-naphthyl) thioprogash thio-1,2,3,4-tetrazole, colorless needles (ethanol), mp, 56-58 ° C;

1-methyl-5- 3- (2-quinolyl) thiopropsh1 tyo-I, 2,3I4-tetrazole, pale yellow needles (methanol), so pl. VT-HEE;

| -methyl-5 (4-phenylthiobutyl) thio- -1,2,3,4-tetrazole, colorless prisms (ethanol), so pl. 51.5-53 ° C;

1-methyl-5- (4- (2gcarboxyphenyl) thiobutyl thio-1,2,3,4-tetrazole, pale yellow prisms (ethanol), mp 143.5-144.5 C:

1-methyl-5- 4- (2-methylphenyl) thioutesh) thio-1,2,3,4-tetrazole, colorless liquid, n "1.5786;

1-methyl-5- 4- (2-aminophenyl) thio-tityl-thio-l, 2,3,4-tetrazole, yellow liquid, Pr 1.5961;

1-methyl 5- 4- (4-chlorophenyl) thiobu-thylTthio-1, 4-tetrazol, colorless n (liquid, in; Ts5971;

1-metSH1-5 Cz- {2-furylmethyl) thio-

propyl thio, 2,3,4 ttetrazole, brown liquid, 1.5641;

. 1methyl-5- (3-benzylthiopropyl) thio-1, 2,3,4-tetrazole, colorless liquid, 1.5856;

1-methi (4-chloro-benzyl) thiopropyl, 2,3,4-tetrazole, colorless liquid, Pr 1.5858;

1-methyl-5- 3 (4,5-dimethyl-1,2,4-triazol-3-yl) thiopropyl thio-1,2,3,4-tetrazole, colorless prisms (ethanol, hexane), mp . 74-77 C;

1-methyl-5- 3- (quinazolyl-4-one-2-yl thiopropyl) thio-1,2,3,4-tetrazole, colorless flakes (ethanol-hexane), m.p. 132.5-134.5 ° C;

1-methyl-5- {4- (3N, 4H-1,3,4-benzo-transnazepin-5-one-2-yl) tyobutyl thio- -1,2,3,4-tetrazole, colorless prisms, m.p. (methanol);

(3-eth1thioprosh1l) thio- -1,2,3,4-tetrazole, colorless liquid lOCTCTb, Pd, 1.5385;

1-methyl-5- (3-n-butylthiopropyl) thio-1,2,3,4-tetrazole, yellow liquid, p - 1.5192;

1-methyl-5-3- (4-methyl-2-thiazolyl thiopropyl-Thio-1,2,3,4-tetrazole, colorless liquid, 1.5919;

1-methyl-5-3- (4-pyridyl) tyropropyl thio-1,2,3,4-tetra azole, pale yellow liquid, 1.6017;

1-methyl-5-3- (5-nitro-2-pyridyl) thiopropyl-Thio-1,2,3,4-tetrazole,

pale yellow liquid, n - 1,6289; .

1-methyl-5- 3- (2-amino-4-edetyl-6-pyrimidyl) thio-thio-1,2,3,4-tetrazol, a colorless crystalline powder. (Methanol), m.p. 119-120 C;

i -methylt5- 2- (2-furylmethyl) thioethyl thio-1,2,3,4-tetrazole, pale yellow liquid, Pd - 1.5711;

1-methyl-5-Gz- (2-amino-4-thiazolyl) methylthiopropyl JTHO-1 ,, 3,4-tetrazole yellow prisms (methanol water), m.p. 117-118.5 C;

.1-cyclohexyl-5-З- (1-cyclohexen1 -1,2,3,4-tetrazolate 5-yl) thiopropyl o--1,2,3,4-tetrazole, pale yellow granules (ether-ethanol ), so pl. 88.5-89.5 C;

1-methyl-5-Gz- (1-phenyl-1,2, 3,4-β-tetrazol-5-yl) thiopropyl thio 71,2,3,4-tetrazod, colorless. NpH3t «ii (ethanol ligroin) m.p. 89-90,

1-metsht-5-5- (1 metshg-1,2,3,4-tetrazol-g5-yl) thiopentyl thio-1,2,3,4-tetrazole, colorless prisms (ethanol.}, T mp 64-65 ° C;

1-methyl-5- 6- (1-methyl-1,2,3, 4-tetrazol-5-yl) thiohexyl thio-1j2,3,4-tetrazole, colorless primal (acetone), m.p. ., 5 С .; . .

1-methyl-5-f2-methyl-3 - (- metshg- -1,2,3,4-: tetras6l: 5-yl) thioprosh lStio- -1,2,3, 4-tetrazole, colorless. Prisms (ethanol), so pl. 87-89.5 C;

1-methyl-5-z-methyl-3- (1 methyl--1,2,3,4-tetrazol-5-yl) thiopropsi thio--1,2,3,4-tetrazole, colorless needles (ethanol) m.p. 68.5-70.5 ° C;

1-methyl-5- 2-methyl-3- (2-pyridyl) thioproshi thio-1, 4 heterozole, pale yellow liquid, "1.5936;

1-metshg-5- 4- (A-methoxy-feshsh) tyobutyl thio-1,2,3,4-tetrazole, colorless liquid, NMR (90 MTtt, HSCS), J 1.50-2.20 (4H, multi- happet)} 2.83 (2H, triplet, J 6 Hz); (2H, triplet J 6 Gu); 3.77 (SA, singlet); 3.87 (SA, singlet); 6.82 (2H, triplet, J 9 Hz); 7.32 (2H, dugshet, J ..- -9 Hz).

Example 63, 2-Amino-4-methyl-: -6-chloropyrimidine (1.43 g) and thiourea (0.8 g) were dissolved in ethanol (50 ml), the mixture was heated under reflux for 2 hours. After cooling, the precipitated crystals are filtered and dried. The crystals were dissolved in ethanol (50 ml) and added to a solution of 1-methyl-5 (3-chloropropyl) thio-1,2,3,4-tetrazole (1.73 g) in 10% aqueous sodium hydroxide solution. (5 ml), after which the mixture is refluxed for 4 hours. Ethanol is distilled off, water is added to the residue and the mixture is extracted with chloroform. The extract is washed with a saturated aqueous solution of sodium chloride and dried over magnesium sulfate. After distilling off the chloroform, the residue is purified on a column (C-200 Vakogel, eluent: chloro-pm-methanol 50: 1), then recrystallized from methanol, to obtain 1-meth-5-3- (2-amino-: -4-methyl- 6-pyrimidyl) thiopropyl thio- -1,2,3,4-tetrazole (0.7 g) as a colorless crystalline powder so pl. 119-120 ° C; . . .

th 1 number, N 32,99

C.nH..N, S,

%: C 40.40; H 5.05;

MO

Found,%: C 40.28; H 4.87; N 33,10

Example 64 In Example 63, the following compounds were obtained:

 1-methyl-5- 2- (2-pyridyl) thioethyl thio-1,2,3,4-tetrazole, colorless prisms, t, sh1, 77-79.5 s (ethanol);

1-methyl-5- 4- (2-pyridyl) thiobutyl thio-1,2,3,4-tetrazole, pale yellow prisms, m.p., 49-51, (ethanol-water);

1.-yteyl-5-5- (2-pyridyl) thiopentyl1 thio-1,2,3,4-tetrazole, colorless liquid, tvj) 1,5853;

1-methylt-5- b- (2-pyridsh1) thiohexythi-i, 2,3,4-tetrazole, colorless prisms, m.p., 58-60 s (ethanol) ;,

1-methyl-5- 3- (4-methyl-2-pyrimidyl thiopropyl thio-1,2,3,4-tetrazole, colorless liquid, 1.5853;

1-methyl-5- 3- (2-benzimidazolyl) thiopropyl thio-1,2,3,4-tetrazole, colorless needles (ethanol), t, mp, 137-139 ° C;

1-methyl-5- 3- (3,5-di-tert, butyl-4-hydroxyphenyl) thiopropyl thio-1,2,3,4-tetrazole, pale yellow needles (methanol-water), t. square 76-77 C;

1-methyl-5-3- (5-amino-1,3,4-thiadiazol-2-yl) thiopropyl thio-, 2,3,4-tetrazol, colorless prisms (ethanol), t, Sh1. 120.5-122 ° C;

e 5 0

five

1-methyl-5- 3- (5-methyl-1,3,4-oxadiazol-2-yl) thiopropyl thio-1,2,3,4-tetrazole, colorless liquid, 1.5644;

1-methyl-5- 3- (p-naphthyl) thiopropyl thio-1, .2,3,4-tetrazole, colorless needles (ethanol), mp. 56-58 C;

1-methyl-5-Z- (2-quinolyl) thiopropyl thio-1,2,3,4-tetrazole, pale yellow needles (methanol), mp, 87-89 ° C;

1-methyl-5- (4-phenylthiobutyl) thio- -1,2,3,4-tetrazole, colorless prisms (ethanol), so pl. 51.5-53 ° C;

1-methyl-5- 4- (2-carboxyphenyl) thiog butyl thio-1,2,3,4-tetrazole pale prism (ethanol), so pl. 143.5-144.5 C;

1-methyl-5- 4- (2-methylphenyl) thiobutyl thio-1,2,3,4-tetrazole, colorless liquid, Pr 1.5786;

1-methyl-5- 4- (2-aminophenyl) thiobutylZthio-, 2,3,4g tetrazole, yellow liquid, Pr 1.5961;

1-methyl-5- 4- (4-chlorophenyl) thioboux1 thio-1, 2,3,4-tetrazole, colorless liquid, Pr 1.5971;

-methyl-5- 3- (2-furiAmethyl) thiopropyl thio-1,2,3,4-tetrazole, brown liquid, 1.5641;

1-methylg-5- (3-cyclopentylthiopropyl) hyo-, 2,3,4-tetrazole, pale yellow liquid, Pp 1.5469;

1-methyl-5-3- (2-pyridylmethyl) thiopropyl thio-1, 2,3,4-tetrazole, brown liquid, p 1.5820;

1-methyl-5-Z- (4-methyl-2-thiazolyl) thiopropyl thio-1,2,3,4-tetrazole, colorless liquid, 1.5919;

1-methyl-5- 3- (4-pyridyl) thiopropyl thio-1,2,3,4-1 interrazole, pale yellow liquid, n - 1.6017;

1-methyl - 5-З- (5-nitro-2-pyridsh1) thiopropyl thio-1,2,3,4-tetrazole, pale yellow liquid, 1, б289 |

1-methyl-5- (furylmethylthioethyl) thio- -1,2,3,4-tetrazole, pale yellow liquid, Pp 1.5711 ;.

1-methyl-5- {3- (2-amino-4-thiazolyl) methyl thiopropyl thio-1,2,3,4-tetra azole, yellow prisms (methanol-water), so pl. 117-118.5 ° C;

1-cyclohexyl-5- 3- (1-cyclohexyl -1,2,3,4-tetrazol-5 yl) thiopropyl thio-1, 2,3,4-tetrazole, pale brown granules (ether-ethanol) m.p. 88.5-89.5 C;

1-methyl-5-3- (1-phenyl-1,2,3,4-β-tetra azol-5-yl) thiopropyl thio-1,2,3,4-tetrazol, colorless prize 1 1 (ethanol - ligroin), so pl. 89-90,

1-methyl-5-3- (1-methyl-1,2,3,4-tetrazol-5-yl) thiopentyl thio-1,2,3,4-tvt-razol, colorless prisms (ethanol) m.p. 64-65 ° C;

1-methyl-5-b- (1-methyl-1,2,3,4-tetrazol-5-yl) thiohexyl thio-1,2,3,4-tetrazol, colorless prisms (acetone), m.p. 91-93 ° Cj

1-methyl-5- 2-methyl-3- (1-methyl--1,2,3,4-tetrazole 5-sh1) thiopropyl thio- -1,2,3,4-tetrazole, colorless prisms (ethanol) m.p. 87-89.5 s;

1-methyl-5- 3-methyl-3- (1-methyl-1,2 3,4-tetrazol-5-yl) thiopropy thio- -1,2,3,4 tetrazole, colorless needles (ethanol), t. square 68.5-70.5 C;

1-methyl-5- 2-methyl-3- (2-pyridyl) thiopropyl thio-1,2,3,4-tetrazole, pale yellow liquid, 1.5936

1-methyl-5-4- (4-MeTokcH eHmi) thio-butyl thio-1,2,3,4-tetrazole, colorless liquid, NMR (90 MHz, CDCI), 5: ppm 1.50-2.20 (4H, multiplet); 2.83 (2H, triplet, J 6 Hz); 3.30 (2H, triplet, J 6 Hz); 3.77 (ZN, singlet 3.87 (ZN, singlet); 6.82 (2H, doublet, J 9 Hz); 7.32 (2H, triplet, J, 9 Hz);

1-methyl-5- (3-cyclohexylthiopropyl) thio-1,2,3,4-tetrazole, colorless liquid, iij 1.5433;

1-methyl-5-W- (2-pyridyl) thiopropyl thio-1,2,3,4-tetrazole, pale yellow liquid, Ai 1.6022;

1-cyclohexyl-5- (3-ethylthiopropyl) thio-1,2,3,4-tetrazole, colorless liquid, n j) 1.5433;

 1-methyl-5-3- (1-methyl-1,2,3,4-tetrazol-5-yl) thiopropyl thio-1,2,3,4-tet7 dispersed, colorless prisms (ethanol), t .pl. 141.5-143,

1-methyl-5- 4- (1-methyl-1,2,3,4-tetrazol-5-yl) thiobutyl thio-1,2,3,4-tetrazole colorless needles (ethanol), mp . 22-123 ° C;

1-phenyl-5- 4- (1-phenyl-1,2,3,4-tetrazol-5t yl) thiobutyl thio-1,2,3,4-tetrazole, colorless needles (ethanol-chloro form), . m.p. 127-128.5 ° C; . . .1-methyl-5- 3- (1-cyclohexyl--1,2,3,4-tetrazol-5-yl) thiopropyl thiog-1,2,3,4-tetrazole, pale yellow liquid, nj, 1 , 5653;

1-phenyl-5- 3- (1-phenyl-1,2,3,4-tetrazol-5-yl) thiopropyl thio-1,2, 3j4-tetrazole, colorless needles (methanol-chloroform), mp . 81-82 ° C;

1-methyl-2- 3- (1-metsh1Imidazol-2- -yl) tyropyl thio-, 2,3,4-tetrazole, colorless needles (ether), tl. 59.5-60,

Example 65. 1-Methyl-1,2,3,4-tetrazol-5-yl-bromobutyl sulfoxide (2.7 g) and 1-methy-1-5 mercapto-1,2,3,4-tetrazole (1.4 d) dissolve in acetone (50 ml) and potassium carbonate (1.4 g) is added to the solution, then the mixture is heated under reflux for 2 hours. After distillation of the acetone, water is added to the residue and the mixture is extracted chloroform. Hdorofort; The solution is washed with a saturated aqueous solution of sodium chloride and the magnesium sulfate is dried. Chloroform is distilled off, the residue is purified on a column (Kieselgel 60, eluent: chloroform-methanol 100: 1) to give H-methyl -1,2,3,4-tetrazolt 5-yl-4- (1-methyl -1,2, 3,4-tetrazol-5-yl) thiobutylsulfoxide (1.5 g) as a colorless liquid, Pp 1.5660.

Calculated,%: C 31.78; H 4.67; N 37.06

Cglli NgOSj

Found,%: C 31.65; H 4.72; N 37.11.

Example 66. In Example 65, the following compounds were prepared:

1-methyl-1,2,3,4-tetraz6l-5-Sh1- - (1-methyl-1,2, S, 4-tetrazol-5-yl) thiobutylsulfone, colorless needles (ethanol-chloroform) m.p. 70-72 C;

4- (2-pyridyl) thiobutyl- 1 -methyl- -1,2,3,4-tetra-azol-5-yl-sulfoxide, pale yellow liquid, 1.5893;

1-methyl-1,2,3,4-tetrazol-5-yl-3- - (5-methyl-1,3,4-oxadiazol-2-WI) thio propylsulfonic, pale yellow liquid. 1.5620;

1-methyl-1,2,3,4-tetrazol-5-yl-3- (2-pyridyl) thiopropyl sulfoxide, pale yellow liquid, 1.5997;

1-methyl-1,2,3,4-tetrazol-5-sh1-3-methyl-3- {1-methyl-1,2,3,4-tetrazol-5-yl) thiopropyl sulfoxide, colorless liquid, Hji 1.5680;

1-methyl-1,2,3,4-tpr ae ol-5-yl-3- -methyl- (5-methyl-1,3,4-oxadiazol-5-yl) thiopropyl sulfoxide, uniformly yellow liquid, p, - 1.5580; . ,

1-methyl-1,2,3,4-tetrazol 5- "l-4 - (2-pyridyl) thiobutylacetate, colorless to liquid, 1.5643.

Example 67; 2-Chloropyridine (1.13 g) and thiourea (0.8 g) are dissolved in ethanol (50 ml), the mixture is boiled with a reverse fridge for 1 hour. After cooling, the precipitated crystals filtered and dried. The crystals were dissolved in ethanol (50 ml), and 1-methyl-1,2,3,4-tetrazole-5-yl-4-bromobutyl sulfoxide (2.4 g) and a 10% aqueous hydroxide solution were added to the solution. (10 ml), the mixture is refluxed (for 4 hours. After ethanol is distilled off, water is added to the residue, the mixture is extracted with chloroform. The extract is washed with a saturated solution of sodium chloride, dried with magnesium sulfate. Chloroform is distilled off, the residue purified on a column (Keisegel 60, eluent-chloroform) to obtain 4- (2-pyridyl) thiobutyl-1-methyl-, 2,3,4-tetrazol-5-yl sulfoxide as a yellow liquid, 1.5989.

Calculated,%: C 44.42; H 5.08; N23.55

C, E ,,,.

Found,%: C 44.32; H 5.12; N 23.39.

Example 68. In Example 67, the following compounds were prepared:

1-methyl-1,2,3,4-tetrazol-5-yl-4- - (1-methyl-1,2,3,4-tetrazol-5-yl) thiobutyl sulfone, colorless needles

(ethanol), so pl. 70-72 ° C;

3- (1-methyl-1,2,3-, 4-tetrazol-5-yl) thiopropyl-2-pyridine sulfoxide, colorless prisms (ethanol), mp. 90.5 ° C;

3- (1-metip-1,2,3,4-tetrazole-5-Sh1) thiopropsh-1-2-pyridylsulfonI; colorless prisms (ethanol), so pl. 98.51 & 1 ° C; ;

The pharmacological activity of the compounds of the indicated general formula according to the invention was investigated for the following compounds.

1.1-Methyl-5- 4- (1-methyl-1,2,3,4-β-tetrazol-5-Sh1) thiobutylSthio-1,2,3,4-β-tetrazole.

2.1-Methyl-5-З- (2-pyridyl) thiopropyl 1 thio-1, 2,3,4-tetrazole.

3,1-Methyl-g5- (3-cyclohexylthioproth drank) thio-1,2,3,4-tetrazole.

4.1-Methyl-5- (3-methyl-1,3,4-β-yxadiazo -2-yl) thiopropyl thio- -1,2,3,4-tetrazole. .

. 5. 1-Methyl-5 -.) - (- methyl-1, 2,3,4-β-hetasol-5-yl). Thiopentyl thio-1,2,3,4-tetrazole,. .

. 6. 1-Methyl-5- 3- (1-methyl-1,2,3,4-tetrazol-5-yl) thio-3-methylpropyl thio -1,2,3,4-tetrazole.

7.1-Methyl-5- (3-eth1thiopropyl) thio- -1,2,3,4-tetrazole.

8.1-Methyl-5- (3-butylthiopropyl) thio-1,2,3,4-tetrazole.

9.1-Methyl-5- 2-methyl-3- (1-methyl--1, 2,3,4-tetrazol-5-yl) thiopropyl, thio--1,2,3,4-tetrazole.

10.1-Methyl-5- (3-phenylthiopropyl) thio-1,2,3,4-tetrazole.

11.1-Methyl-5- 3- (1-methylimidazol--2-yl) thiopropyl thio-1,2,3,4-tetrazole

12.1-Methyl-5-z- (5-amino-1,2,3,4-β-thiadiazol-2-yl) thiopropyl thio-1,2,3, -tetrazol.

13.1-Methyl-5- 3- (4-methyl-2-pyrimidyl) thiopropyl thio-1,2,3,4-tetrazole

14.1-Metsh1-5- 3- (3-hydroxy-2-pyridyl) thiopropyl thio-1,2,3,4-tetrazole.

15.1-Methyl-5-W- (4,5-dimethyl--1,2,4-triazol-3-yl) thiopropyl thio--1,2,3,4-tetrazole.

16.5- (Zg-Phenylthiopropyl) thio-1, 2,

3,4-tetrazole. I

17.1-methyl-5-3- (2-amino-4-thiazolyl) methylthiopropyl thio-1,2,3,4-tetrazol.

18.1-Methyl-5-З- (2-quinolinyl) thiopropyl thio-1,2,3,4-tetrazole.

19.1-Methyl-5- 3- (2-benzimidazolyl) thiopropyl thio-1,2,3,4-tetrazole.

20.1-Metsh1-5-Z- (2-yaphenyl) thiopropyl thio-1,2,3,4-tetrazole.

21.1-Methyl-5- 3- (2-furyl) methylthiopropyl thio-1,2,3,4-tetrazole.

22.1-Methyl-5- (3-benzylthiopropyl) thio-1,2,3,4-tetrazole.

23.1-Methyl-5- 3- (2-pyridyl) methyl thiopropyl thio-1,2,3,4-tetrazole.

24.1-Methyl-5- 3- (4-methyl-2-thiazo.-lil) thiopropyl thio-J. 2,3,4-tetrazole

25.1-Ketil-5-5- (4-pyridyl) thiopropyl thio-1, 2,3,4-tetrazole.

26.1-Methyl-5- (2-amino-6-methyl-4-pyrimidyl) thiopropyl thio-1,2,3,4-terazole.

27,1-Methyl-2-A- (1-methyl-1,2,3,4-tetrazol-5-yl) thiobylyl isothiourea (hydrobromide).

28,1-Methyl-5- (4-phenylthiobutsch1) thio-1,2,3,4-tetrazole.

29,1-Methyl- 5-4- (4-oxo-3, hydroquinazolin-2-yl) thiooctyl thio- -1,2,3,4-tetrazole.

30,1-Cyclohexyl-5- (3-ethylthio-propyl thio-1,2,3,4-tetrazole.

31.1 1 methyl 5- 2- (2-pyridyl) thio-methyl thio-1,2,3,4-tetrazole,

32,1-fetil-5- 5- (2-pyridshl) thiophene I and o-l, 2,3,4-tetrazole ,.

33,1-Metshg-5-g b- (2-pyridyl) thiohexyl thio-1,2,3,4-tetrazole,

34,1-Methyl-5- 2-methyl-3- (2-pyridyl) thiopropyl thio-1, 2,3,4-tetrazole,

35,1-Methyl-5- 2- (1-methyl-1,2,3,4-β-tetrazol-5-yl) thiosyl thio-1,2,3,4-β-tetrazole.

.- .. 36, I-Methyl-5-b- (1-methyl-1,2,3,4-tetrazol-5-yl) thiohexyl thio-1, Z, 3,4-tetrazole.

37,1-Methyl-5- 3- (1-methyl-1,2,3,4-β-tetrazol-5-yl) thiopropyl thio-1,2,3,4-β-tetrazole,

38,1-Feiil-5-Z- (1-phenyl-1,2,3,4-tetrazolate 5-yl) thiopropyl thio-1,2,3,4-tetrazole,

39,1-Methyl-5-3- (1-phenyl-1,2,3,4-β-tetrazol-5-yl) thiopropyl thio-1,2,3,4-tetrazole.

40,1-Methyl-5- 3- (5-nitro-2-pyridyl) thiopropyl} thio-1,2,3,4-tetrazole,

41,1-Methyl-5- З- (4-chlorbeisyl) thiopropyl thio-1,2,3,4-tetrazole,

42,1-Methyl-5-Z-methyl-3- (5-methyl-g1,3,4-oxadiazol-2-yl) thiopropyl thio- -1,2,3,4-tetrazole.

43,1-Methyl-1,2,3,4-tetrazol-5-yl-3-methyl-3- (5-methyl-1,3,4-oxadiazol-2-yl) thiopropyl sulfoxide.

44,3- {1-Methyl-1,2,3,4-tetrazol-5- -yl) thiopropyl-2-pyridyl sulfoxide,

45,1-Methyl-1,2,3,4-tetrazol-5-yl-4- (2-pyridip) thiobutyl sulfoxide.

46,4- (1-Methyl-1,2,3,4-tetrazole-5-Sh1) thiobutyl-1-methyl-1, 2,3, 4-tetrazol-5-yl-sulfoxide.

47, 4- (1-Methyl-1,2,3,4-tetrazol-5-yl) thiobutyl-1-methyl-1, 2, 3, 4 tet-razol-5-yl sulfone t

48.3- (1-Methyl-1,2,3,4-tetrazol-5-yl) thioprosh-2-pyridylsulfone,

j

0

five

0

five

0

49,1-Methyl-I, 2,3,4-tetrazol-5-sh1-3-methyl-3- (I-methyl-1,2,3,4-tetrazol-5-yl) thiopropyl sulfoxide,

50,1-Methyl-5- (3-propionylpropyl) thio-I, 2,3,4-tetrazole,

51, I-Phenyl-5- (Z-beisylpropyl) thiol 1,2,3,4-tetrazole,

52,1-Cyclohexyl-5- (3-cyclohex-sgshcarbonylpropyl) thio-1,2,3,4-tetrazole,

53,1-Methyl-5- (3-benzoylpropyl thio -1,2,3,4-tetrazole,

54,1-g Methyl-5- 3- (2-thenoyl) propyl thio-1,2,3,4-tetrazole,

55.1-Meters 1-5-3- (2-furoyl) propyl thio-1,2,3,4-tetrazole,

56,1-Methyl-5-z- (3,4-dimethoxybenzoyl) popyl thio-1,2,3,4-tetra azole,

37. 1-Metshg-5- (3-benzylcarbonyl-propyl) thio-1,2,3,4-tetrazral,

58,1-Metershg: 5- 3- (4-methylaminobenzoyl) propylthio-1,2,3,4-tetrazole,

59.1 Methyl-5- {3-acetal-1-trace-1) thio--1,2,3,4-tetrazole,

60,1-Methyl 5- 3- (P-phenyl-methylcarboyl) pr sawdio-1,2,3,4-tetra azole,

61,1-Methyl-5- (benzoylmethyl) thio- -1,2,3,4-tetrazole,

62,1-Methyl-5- (3-pentanoylpropyl) thio-1,2,3,4-tetrazole,

63.1-Methyl-5- 3- (4-methoxybenzoyl) propyl thio-1,2,3,4-tetrazole,

64,1-Methyl-5- 3- (5-metsh1-2-telenoyl) propyl thio-1,2,3,4-tetrazole,

65.1-Methyl-5- (3-cyclopentsh1kar-bonylpropyl) thio-1,2,3,4-tetrazole,

66,1-Methyl-5-3-cyclohexylcarbonylpropyl) thio-1,2,3,4-tetrazole,

67.1-Methyl-5-acetylmethyl) thio-I, 2,3,4-tetrazole,

68.1-Methyl-5-z- {4-hydroxybenzoyl) propyl thio-1,2,3,4-tetrazole,

69.1-Methyl-5 p- (4-ethylbenzene) propyl thio- 1, 2, 3, 4-tetrazole.

I

70.1-Methyl-5- | 3- (4-chlorobenzoyl propyl) thio-1,2,3,4-tetrazole,

71,1-Methyl-5- (4-benzoylbutyl) thio-.-1,2,3,4-tetrazole,

72.1-Methyl-5- (5-benzostentil) thio-1,2,3,4-tetrazole,

73.1-Methyl-5- 3- (2 pyrrolyl) carbonyl propyl thio-1,2,3,4-tetrazole,

74.1-Methyl-5- 2- (2-pyridyl) carbonylpropyl thio-1,2,3,4-tetrazole,

75,1-Methyl-5- 3- (5-chloro-2-teno-ip) propyl thio-1,2,3,4-tetrazole.

76.1-Methyl-5 3- (5-carboxymethyl--2-furoyl) propyl} thio-1,2,3,4-tetrazole

77.1-Phenyl-5- (3 cyclohexylcarbonylpropyl) thio-1 2,3,4-tetrazole,

78.5-Acetylmethylthio-1,2,3,4-tag-solution.

79.1-Methyl-5-Гз- (4-butoxybene-yl) propyl thio-1,2,3,4-tetrazole.

80.1-Methyl-5- 3- {4-methylt-5-thiaoolyl) carbonylpropyl thio-1,2,3,4-gamma

split,

81.1-Methyl-5- (3-cyclohexylcarboxylic iopropyl) thio-1,2,3,4-tetrazole.

, 82. 1 Metshg-5- 3- (H et 11l-N-propionilamio) propyl thio-1, 4-tetrazole,

83.1-Methyl-5- 3 - (- methyl-11-ace-, tylaminopropyl) thio -1,2,3,4-tetrazole,

84.l-Methyl-5- 3- (N, N-diethylamino propyl thio-1,2,3,4-t ester azole.

85.1 Ch1ethyl-5- 3- (phtal € Ido) propyl thio-1,2,3,4-tetrazole,

86.1-Methyl-5- (3-acetylaminopropyl) thio-1,2,3,4-tetrazole.

  87. 1-Metsh1-5- (3-propioiyl-iamio-propyl thio-1,2,3,4-t. Teraz6l.

88.1-Methyl-5- (3-benzosch1 and propyl) thio-1,2,3,4-tetrazole.

89.1-Methyl-5- 3- (N-methyl-K-cyclohexylcarboxylaminopropyl thio-1,2,3, -tetrazol.

90.1-Methyl-5-3- (N-ethyl-N-r cyclohexylcarbonylamino) propyl thio-1,2,3 4-tetrazole,

91.1-Metshg-5- 3- (H-ethyl-K-benzoylamidio) propyl thio-1,2,3,4-tetrazole.

92.1-Methyl-5-3- (K-ztsh1-1b cyclo-pentylcarbonylamino) propyl thio-1,2, 3 4-tetrazole.

93.1-Methyl-5-z- (L-etsh1-H- (2-furylcarbonyl) aminopropyl thio-1,2,3,4-tetrazole.

94.1-Methyl-5-З- (L-beisyl-L-propylamino) propyl thio-1,2,3,4-tetrazole

95.1-Methyl-5- (3-hexaioyl-amus-propyl thio-1,2,3,4-tetrazole.

96 i 1-Methyl-5-z- (4-methoxybenzoyl-ylmino) propyl thio-1,2,3,4-tetrazole.

97.1-Phenyl-5- 3- (H-ztil-L-benzoylamino) propyl thio-1,2,3,4-tetrazole.

98.1-Methyl-5- (2-pyridylmethyl) thio-I, 2,3,4-tetrazole.

99. (1-methyl-1,2,3,4-tetrazo-5-ip) thiopropsh1} -3-methylthiourea.

100.1-Methyl-3- (5-methylamino--1,2,3,4-tetrazol-1-yl) propyl thio--1,2,3,4-tetra ol.

101.1-Methyl-5- 3- (3-methylguanidio) propyl thio-1,2,3,4-tetrazole. (iodhydrate).

102.1-Amino-2-methyl-3- 3- (1-methyl-1, 2,3,4-tetrazol-5-yl) thiopropyl guaiidine (iodohydrate).

103.1-metip-5-cyclohexylmethyl-thio-1,2,3,4-tetrazole.

104.1-Methyl-5- (4-methoxybenzyl) thio-1,2,3,4-tetrazole.

Pharmacological Test I. The pharmacological activity of the compounds of general formula I is investigated using ligat overlay methods on the pyloric part of the gland in rats, which is the most well-known method for investigating inhibitory activity on the secretion of gastric juice. The tests were carried out on Wistar rats, weighing g, which were not fed for 24.44.

Test compounds were administered 30 minutes before applying a ligature to the pyloric part of the stomach in doses of 100 mg / kg with subcutaneous injection of compounds 37, 38, 50, 51 and 52, at doses of 200 mg / kg with subcutaneous administration of compounds 105 and 106 and in a dose of 100 mg / kg with the introduction into the duodenum of other subjects tested. After 4 hours after applying the ligature, the volume, total activity and pepsin activity of the gastric juice is measured. Saline solution is used as a control sample and injected instead of the test compound, the percent inhibition for the test compound is calculated on the basis that the inhibitory activity of the control sample equal to 0. The results are shown in v, Table. 1. (value of the inhibitory index, + 10-50; ++ more than 50).

Table

++ ++

+ 4

711212324

Continuation of table 1

72 Continuation of table. I

731212324

Continuation of table 1

74

Continued table. one.

in the case of compounds 3, 4, 6, 15 to 27, and with co-titration of 1x x 10 mol in the case of other compounds. Only a solvent is used as a control sample (pa

 (-IAP control animals. Inhibitory indicator) “JOO. ".

The results are shown in Table. 2. The following are used.

CMC), entered similarly. the stress inhibition index of the stress test for the tested compounds is calculated using the following equation, V

(PL for animals to which test compounds were administered)

Yap control animals

designation for inhibition rate, Z: "30-60, ++ more than 60.

Table 2.

++

4 - +++

++ f +

Pharmacological test 3: ulcers caused by indomethacin.

Male Wister rats weighing 170 g were left without food for 24 hours, after which indomethacin was administered to animals, subcutaneously at a dose of 20 mg / kg as a suspension in a mixture of 0.5% CMC and a non-large amount of Tween-80 polyoxyethylene sorbitan-oooleate). After 5 hours, the animals are sacrificed and the stomach is removed. 8 ml of 10% formalin is introduced into the stomach and allowed to settle. The stomach is then opened for a long time and the length of each ulcer lesion is measured. Based on the obtained results, the index of inhibition of the ulcer lesion caused by indomethacin is calculated for each of the tested compounds according to the calculation scheme outlined in pharmacological test 2, the test compound is administered orally to rats at doses of 100 mg / kg in the form of a 0.5% suspension in CMC 30 minutes before the administration of indomethacin.

The results are shown in Table. 3, the inhibition rate, is indicated as follows,%: + 30-60, ++ more than 60.

Editor Oh, Kolesnikova

Compiler A, Orlov

Tehred A. Babinets Corrector V, But ha

653/62.

Circulation 379 Subscription VNIIPI USSR State Committee

for inventions and discoveries 113035, Moscow, Zh-35, Raushsk nab, 4/5

Branch PIP Patent, Uzhgorod, st. Project, 4

Continuation taol.2

++

; ++ ++

. ++ ++

20

Table 3

Claims (1)

METHOD FOR PRODUCING TETRAZOL DERIVATIVES OR THEIR PHARMACOLOGICALLY ACCEPTABLE ACID-ADDITIVE SALTS. (57) Method for the Preparation of • Hetrazole Derivatives of the General Formula N — N X JL-SIOVA-Wm-Bi N where R is hydrogen, C, —C ₆ ~ alkyl, phenyl. or c _? -C ₈ cycloalkyl; X is a carbonyl group or a group -S (0) „; ΐ and η = 0 or 1, or 2; m is 0 or 1; A — C, —C _in —apkylene; R, - C, -C ₆ -alkyl, C ₃ -C _a cycloalkyl _l naphthyl group of formula -C (= NH) NHR _Z (where R ₂ - C, -C ₆ -alkyl phenylalkyl wherein the alkyl has Ιό carbon atoms and wherein the phenyl nucleus may be substituted by halogen, phenyl having ί-W substituent from halo, ί C (-C _£ alkyl, C, - C ₆ -alkoxy, C <-C ₆ alkanoylamino, C ^ -Cg- alkyl substituted with heterocyclic group which may have a substituent selected from among a C ₄ - C _f -alkyl or amino wherein getero.slicheskaya group is selected from among the pyridyl, furyl, thiazolyl, the heterocyclic group with 1-4 eteroatomami from among nitrogen, oxygen or sulfur atoms which may have 1-2 substituents selected from among C <-C ₆ -alkyl, halogen, carboxyl, oxo, amino, C _t -C ₆ -apkoksikarbonila, hydroxyl, amino, nitro, phenyl , Cj-C _e cycloalkyl or C _(-C alkylamino _minutes, and in the case where m «· O, R, can also be a group of formula -NR ₃ R _4, where R -? is hydrogen, C, -C _6- alkyl or phenyl (C, -C ₆ ) alkyl; R ₄ is hydrogen C (-C ₆ -alkyl, -CZNHR _St group where Z is sulfur or an amino group which may be substituted with C <-C ₆ -alkyl; Ry C ^ -Cg-alkyl or amino, or R ₄ ~ tetrazolyl, which may be substituted with C, -C ₆ -alkyl or -N-CO-R ₆ , where R ₆ is C, -C ₆ -alkyl, phenyl , which may have 1-3 substituents from among C <- C _in -alkoxyl, C _? -C ₈ -cycloalkyl, or R * - 5- or 6-membered unsaturated nitrogen or sulfur containing heterocycle, .or R ₄ and R _? together with the common nitrogen atom form a group w = 0, then R ₄ - group -KRjR ₄ , where Rj is hydrogen, Ci-Cg-alkvl, C, -C ₆ -alkoxycarbonyl, or Rj and R ₄ together with a common nitrogen atom form a group, distinguished by the fact that tetrazole is common, provided that when V "1 or kg 2, then m "I and X are sulfur, or their pharmacologically acceptable acid addition salts, n and a. formulas where R has N — N O 1 indicated values; Ζ, is the group Υ, (where Υ ₍ is halogen, mercapto or amidino group), or Ζ, is the group —S- (O) gAY *, in which A, f and Υ ₍ have the indicated meanings, are reacted with a compound of the formula Zj-Y ₂ , where Y ₂ is a mercapto or amidino group in the case when Y is halogen, and Z ₂ is a group - 'A “(X) _m ^_ R _i (where A, X, ώ and R ₍ have indicated values), and when Z * Y, or Z ₂ is a group R _o then Z * is a group - S (0) _t -AY, in the presence of an acceptor of hydrogen halide at a temperature from room temperature to 200 ° C for a time from 30 to 6 h, followed by isolation of the target product in the form of a base or acid addition salt. The priority according to the characteristics of 01.03.80 R is C * -C ₆ -alkyl, phenyl, or C jC _g -cycloalkyl; R, - C, -C ₆ -alkyl, phenyl, C _? —Cg — cycloalkyl, a pyridine heterocyclic group * yielded, substituted or unsubstituted thiazolyl or tetrazolyl, or when 0; X is sulfur; A, w = O or 1; I Z *, Z ₂ , Y * and Y _t are all values, 16.099.80 R is C, -Cg alkyl; phenyl R * is the group —N RgR ₄ , where R is the water RUB genus, C * -C _{6 is} alkyl, phenyl (C, -C ₆ ) is alkyl / R ₄ is hydrogen, C, -C _{6 is} alkyl, the group CORg, where Rg is Cj-Cg-alkyl, phenyl, Cj-Cj-cycloalkyl, 5-6 membered unsaturated nitrogen — or a sulfur-containing heterocycle, or R _{? and} R ₄ together with a common nitrogen atom form a group m - 1; G - o; A, Z ,, Z ₂ , Y, and Y _{2 are} all meanings; 06,10.80 R - hydrogen, C * -C _e alkyl, 'phenyl, C ₀ -C ₃ -cycloalkyl, R, C _{{-C 6} alkyl, C * -C _in ksyl alkyl, C, ~ C _Q -alkylamino group, hydroxyl, heterocyclic group unsubstituted or substituted; X is carbonyl; m ^W 1 * I '- 1; A, Z ,, Z ₂ , Y * and Y _g are all values.