SU389661A1 - BI •:.:. K1SHIBLIOTSHA I (Federal Republic of Germany) - Google Patents

Description

METHOD OF OBTAINING SULFAMOILPYRIMIDINES

This invention relates to a process for the preparation of sulphamoyl pyrimidines, which can be used in the pharmaceutical industry. A known method for the preparation of sulfamoyl-5-rimidines is by condensation of the corresponding guanidine sulfonyl with malonic dialdehyde. Based on the known reaction, the proposed method for producing sulfamoyl pyrimidines of the general formula

X-C - Y-N- CO-SO 2

f Rij,

NH- I -W-R6

asymmetric carbon atom; same or different, direct bond or methylene group 20; hydrogen or halo, Ci-Cz-alkyl or Ci-C4-alkoxy; hydrogen, Ci-C4-alkyl with pr my

or branched chain, carbo- 25

xyl or alkoxycarbonyl with 1-4 carbon atoms;

same or different, hydrogen or lower ..- alkyl;

Ci-Sat-alkyl C or branched chain; and W - straight C-C-bond or oxygen or sulfur. 3 is that optically

RS R5 Y -X-C-Y-lI-CO-CH-C

R4

where C, X, Y, Ri, R2, Rs, R4, Rs and R have the above meaning, and Q is halogen, mainly chlorine, is treated with guanidine,

where C, X, Y, Ri, R2, Rs, R4, Rs and Rr have the above meaning, condense with a substituted malonic dialdehyde of the general formula

CH-W-Rg

where W and Re have the above meaning, in which the aldehyde groups may also have functional modifications, and the target product is isolated in a known manner as racemate, oltic antipodes or salts. Suitable inorganic or organic bases are used to prepare the salts.

Example 1. 1-Phenylethylamide (5-isopropylthio-2-pyrimid, nyl) - sulfamoyl-phenylacetic acid. 15 g (44.5 mol) of 1-phenylethyl amide 4-chlorosulfo-1-nylphenyl-acetic acid in 70 ml of acetone are added dropwise at a temperature of -5 ° C to a mixture of 11.2 g of guanidine nitrate and 37 g of sodium hydroxide in 40 ml of acetone-water (1: one). After 2 hours, 40 ml of water are added and drying is carried out. 7 g of crude 1-feiyl ethylamide 4-guanidiN are taken out: Osulfonylphenyl acetic acid.

At 0 ° C, 4 g of phosgene are introduced into a solution of 2.8 g of dimethylformamide in 12 ml of toluene, at 5 ° C they are added dropwise to 3.7 g of isopropylmercapto acetaldehyde diethyl acetal, stirred for 2 hours at 65 ° C, toluene is distilled off in vacuum and the residue is neutral B 4 ml of methanol with sodium methylate solution in methanol. The resulting product is added to a solution of 0.9 g of sodium in 20 ml of methanol, diluted with 7 g of sulfoguanidine and heated for 12 hours under reflux. After neutralization with hydrochloric acid (pH 6), the table salt is separated.

the obtained optically active guanidine sulfonyl of the general formula

NH

-NH-d

Ш2

the filtrate is evaporated in vacuo and the residue is dissolved in water. After acidification with hydrochloric acid, a substance is isolated which is once again dissolved in caustic soda and precipitated with hydrochloric acid. The yield of 3.2 g (15%), so pl. 125-129 ° C.

For the synthesis of isopropyl mercapto acetaldehyde diethyl acetal, 48 g (250 mmoles) of acetyl mercito-acetaldehyde diethyl acetal are added to a solution of 12.5 g of sodium in 175 ml of ethanol, heated for 15 minutes under reflux and at a boiling point without further heating, dilute 64.6 g of methyl bromide. After heating under reflux for 1 hour, the solution is concentrated in vacuo, diluted with 300 ml of ice-cold water and extracted with ether

benzene (1: 1). The organic phases are thickened and

distilled residue. Yield 42 g (88%), t. Kip.

90-92 ° C / 3mm.

Example 2. 5- (1-Phenylethylamide (5ethyl mercapto-2-pyrimidinyl) - sulfamoyl phenylacetic acid.

33.8 g (100 mmol) of S - (-) - 1-phenylethylamide of 4-chlorosulfonylphenylacetic acid in 90 ml of acetone at -5 ° C are added dropwise to a mixture of 25.2 g of guanide nitrate and 83 g of sodium hydroxide in 90 ml of acetone -water (1: 1). After 2 hours, 90 ml of water are added, S- (-) .. 1 -phenylethylamide 4-guanidinosulfonylphenylacetic acid is sucked off, dried and prepared. 15 g of crude sulfoguanidy.

At 0 ° C, 9 g of phosgene is introduced into a solution of 6.3 g of dimethylformamide in 27 ml of toluene, at 5 ° C, 7.9 g of ethyl mercapto acetaldehyde diethyl acetal are added, stirred for 2 hours at 65 ° C,

toluene is distilled off in vacuo and the residue is neutralized in 9 ml of methanol with a solution of sodium methylate in methanol.

The resulting malonic dialdehyde derivative is added to a solution of 2 g of sodium in

40 ml of methanol, mixed with 15 g of sulfoheactive sulfohalide of general formula 389661 4