LOSARTAN, COMPOUNDS FOR PRODUCTION THEREOF AND METHODS FOR PRODUCTION THEREOF

摘要

Preparation of an imidazole derivative (I) comprises reacting amide compound (IV) with aldehyde compound (V). Preparation of an imidazole derivative of formula (I) comprises reacting amide compound of formula (IV) with aldehyde compound of formula (V). R 1>R-1a or R-1b; R-1a : a tetrazole compound of formula (II); R-1b : tetrazole protecting groups or phenylene groups of (I) by reaction with a group complementary to R 3>; R 3>a compound containing another phenylene units components (III) of formula (R 3>-R 4>); R 4>tetrazole compound (II), where coupling takes place under the formation of C-C bond between the phenylene group to (I) and the phenylene group of (III); R 5>R 1>; R 6>halo group such as Cl, Br (preferred) or I; and R 7>1-6C alkyl, preferably isopropyl group. Independent claims are included for: (1) amide compound (IV); (2) a preparation of (IV) comprising reacting a phenyl amine compound of formula (VII) with ester compound of formula (VIII) in the presence of Bronsted-base; a preparation of (IV) comprising reacting benzylamine derivative substituted with R 5> at para position, with (VIII) in the presence of a Bronsted base; (3) benzyl-imidazol-methanol compound of formula (XI); and (4) a preparation of losartan or its salts comprising preparing (I) with R-1a, which is a benzyl-imidazol-methanol compound (XI) in which the formyl group is reduced with substituted imidazole group, under conventional manner to a hydroxy methyl group, replacing chlorine on the remained hydrogen atom in the imidazole group produced on usual manner, splitting off the tetrazole protecting group and optionally producing salts of (I). R 10>, R 15>tetrazole compound (II); R 11>1-12C alkyl; and X ->anion. [Image] [Image] [Image].