SU399114A1 - - Google Patents

Description

METHOD OF OBTAINING BENZOLSULPHONYLMOLOVA

one

The invention relates to the field of production of a new beisolsulfonylurea of the general formula

 Е-СО-ННСНгСНгi

or

where R is a pyrimidine of the formula

N

R,

-x

R.

N

4f K,

J

-iX

RI

TO,

where RI is hydrogen, halogen, nonstandard or unsaturated alkyl, alkoxy, hydroxy or amino groups, alkyl, halogen, alkoxy substituted or unsubstituted phenyl group, R2 is alkenyl, alkyl, alkyl, alkoxy substituted or unsubstituted, saturated or unsaturated or unsaturated or unsaturated or unsaturated. or a double-core cycloalkyl group, and the cycloalkyl group or double-core cycloalkyl group contains, as appropriate, a nitrogen atom that can find

used as a compound, having Hiero biologically active properties.

A method of producing benzenesulfonylurea is known by reacting sulfonylurea derivatives with n-cyanates, iminocarbamic acid esters.

The original method is based on a known chemical reaction, but it allows to obtain a new benzenesulfonylurea, which has valuable properties.

The proposed method is that the compound of the general formula

 Vso t

L-CO-KNSNgSNg / -yi2Bz

where R has the indicated meaning, and Rs is a halogen, amino or isocyan group, a residue of a urethane or urea,

are reacted with an amine, urea, isocyanate, or an iminocarbamic acid ester, which contain the Ro group.

Example 1. 4.84 g of 2,6-dimethoxynirimidine-4-carboxylic acid in 50 ml of dry acetone II 3.65 ml of triethnlamp are stirred for 15 mpn at 0 ° C, 2.5 ml are added with stirring for 30 minutes ethyl chloroformate and cool to. To the reaction mass was added 5.21 g of i- (rag, inoethyl) benzene sulfa1.1ide in 50 ml of water, 3.65 ml of trisytiline, and the mixture was agitated for 3 hours at room temperature; acetone is removed by unregulation. The mixture was iodized with dilute hydrochloric acid and the resulting crude product was filtered and recrystallized from ethanol to obtain 6.6 g (2.6-dimethoxprimidine-4-yl-carboxamido) -ethyl-benzene-sulphamide, t.il. 187-189 ° C, which are suspended in 100 ml of acetone and 9.84 ml 2 and. Sodium hydroxide is then added to the reaction mixture at a temperature from 0 to 2.45 g of cyclohexyl isocyanate, stirred for 3 hours at room temperature, diluted with water, filtered to remove non-solvent, and acidified with dilute hydrochloric acid. The precipitate thus obtained is recrystallized from ethanol to give L- {4-p- (2,6-dimethoxypyrimidn-4-ylcarboxamido) -ethyl-beisolsulfoyl} -Clnclohexylurea, m.p. 192-194 ° C.

Example 2. Using the method of Example 1, b-methylirimidii-4-carboxylic acid is converted to N- {4-p- (6-methylphenylmylIDI 4-ylcarboxamido) ethyl-isoisulfonyl) N-cyclohexylurea, T. ill. (after recrystallization from ethanol).

Example 3. 7.89 g of methyl-N- (2-methoxyprimidine-4-ylcarboxamido) -ethyl benzenesulfonyl} -carbama1a in 150 ml of co-ethanol are treated with 2.5 g of ammoniapergidroazepia. The methanol is removed by distillation under an ionizhein pressure and the residue is heated to PO-120 ° C for 30 minutes, obtaining after recrystallization from ethanol 1 - {perhydrasei-1 - yl) - N- {4-p- (2 - methoxy-primidine-4 - ilcarboxamido) -ethyl-benzene sulfoiyl} -urea.

Example 4. 3.16 g of b-chloropyridazine-3-carboxycoic acid is refluxed with 2.2 ml of thionyl chloride in 25 ml of dry benzene for 4 hours. The benzene and excess thionyl chloride are removed by distillation. The residue of the acid chloride in dry dnoxane is added dropwise to a suspension of 4 g l - (: p-amio ethyl) benzene sulphamide in dioxane and dry pyridine (3.74 ml). The mixture is refluxed for 2 hours, the dioxys are removed by distillation. Dilute hydrochloric acid is added to the residue, filtered and crystallized from 95% ethanol. 3 g of (b-chloro-iridazin-3-ylcarboxamido) ethyl-bis-sulfamide, t. Il. 210 ° C. A portion of the calcined compound (1.6 g) was suspended in 3.7 ml of 2n. sodium hydroxide and 50 ml of acetone and 0.89 g of npslohexylnosocyanate is added dropwise at a temperature of about -5 ° C. The mixture is stirred for 3 hours at room temperature, diluted with water and filtered. Filtrate

The acidic acids are acidified with hydrochloric acid.

The residue was recrystallized from dioxia to obtain 1.8 g of J- {4-p- (6-chloro-iridazin 3 - yl carboxamido) ethyl ethylbenzenesulfonyl, N-cyclohexyl moraine, m. 197-199 ° C.

Example 5. 6 - Methoxypyridazine-3-carboxylic acid in 50 ml of dry acetone and 3.65 ml of triethylamine are agitated for 15 minutes at 0 ° C, 2.5 ml of ethyl is added with stirring at -5 ° C for 30 minutes chloroform. Next, 5.21 g of p- (p-amio ethyl) benzenesulfamide in 50 ml of water and 3.65 ppm of triethylamine are added to the reaction mixture. The mixture was agitated for 3 hours at room temperature, the acetone was removed by distillation and the residue was acidified with dilute hydrochloric acid. The precipitate is taken off and recrystallized from methanol to give 7.1 g (6-methoxypyridazine 3-yl carboxamido) ethyl ethyl benzenesulfonamide, m.p. 207 ° C. A part of the obtained compound (6.6 g) is treated as in Example 1, 100 ml of acetone, 9.84 ml 2}). sodium hydroxide and 2.45 g of cyclohexyl isocyanate. The precipitate is subjected to crystallization from ethanod, and 4.6 g of M- {4-p- (6-methoxypyridaz11I-3ylcarboxamido) -ethyl-benzenesulfonyl) N-cyclohexylurea are obtained, mp. 193-195 ° C.

Example 6. Operating according to Example 5, pyridazin-3-carboxylic acid is converted to: N- {4- p- (pyridazin 3-ylcarboxamido) ethylbenzenesulfonyl} -K-cyclohexylurea, m.p. 192 193С (after recrystallization from etapol).

PRI me R 7. Methyl-N- (pyridazin-3-yl-carboxamido) ethylbenzenesulfonyl} carbamate in 150 ml of metaiol is treated with 2.5 g of N-amio yergidrazepina. Methanol is removed by propulsion under reduced pressure and the residue is heated at PO-120 ° C for 30 minutes. After recrystallization from ethanol, N - (perhydrazepin-1 - yl) -M- {4-p (niridazium-3-ylcarboxamido) -ethyl-benzenesulfonylurea is obtained.

Subject invention

The method of producing benzenesulfonylurea of the general formula

B-CO-NNSNOSCH-

SO.NHCONlia

,:

where R is pyrimidium or pyridazine of the general formula

fi L N

;

HI

where Ki is hydrogen, halogen, saturated or unsaturated a; iiULT, alkoxy, oxy or ammonia, alkyl, halogen, alkoxy substituted or unsubstituted phenyl group. 56

Ra - alkenyl, alkyl, alkyl-, alkoxymethyl or two-sic yalkloalkl

schenna or unsubstituted, saturated or group, containing, as required, in

an unsaturated cycloalkyl group or a nitrogen atom, characterized in that it combines a sodic cycloalkyl group, a cycloalkynyl compound of the general formula

R CO-11NSCHCHN - -5i ..- In where R has the indicated meaning, and Cs is a halogen, amine or isocyan group, a residue of a urethane or urea, is reacted with ammonium, chevine, isocyanate or ester

399 and 4

An iminocarbampnol 1a slot containing the above-mentioned R-rpynny, followed by isolation of the desired product as a base or salt in a known manner,