4-(BENZIMIDAZOLYL-METHYLAMINO)BENZAMIDINE SYNTHESIS METHOD

摘要

FIELD: chemistry.;SUBSTANCE: invention relates to a method for synthesis of substituted 4-(benzimidazol-2-ylmethylamino)benzamidine of formula (I) or its physiologically compatible salt, in which R₁ is a C₁-C₃alkyl group, R₂ is a R₂₁NR₂₂ group, where R₂₁ denotes a C₁-C₃alkyl group substituted with a C₁-C₃alkoxycarbonyl group, and R₂₂ denotes a pyridinyl group, and R₃ is a C₁-C₈alkoxycarbonyl group having thrombin inhibiting and thrombin clotting time prolonging activity. The method involves a step (a) where phenyldiamine of formula (II) in which R¹ and R² assume values given for formula (I), reacts with 2-[4-(1,2,4-oxadiazol-5-on-3-yl)phenylamino]acetic acid. At step (b), the obtained product of formula (III), in which R¹ and R² assume values given for formula (I), is hydrogenated and then at step (c), if necessary, the obtained product of formula (I), in which R³ is hydrogen, reacts with a compound of formula R³-X (IV), in which R³ assumes values given for formula (I), and X denotes an acceptable leaving group, and then converted to a physiologically compatible salt if necessary. The invention also relates to novel intermediate products - formula (III) compound, in which R¹ and R² assume values given for formula (I), as well as to 2-[4-(1,2,4-oxadiazol-5-on-3-yl)phenylamino]acetic acid, 4-(1,2,4-oxadiazol-5-on-3-yl)aniline and toluene sulphonate N-(2-pyridinyl)-N-(2-ethoxycarbonylethyl)amide 1-methyl-2-[N-[4-amidinophenyl]aminomethyl]benzimidazol-5-yl carboxylic acid.;EFFECT: agents are highly effective.;12 cl, 2 dwg, 6 ex