New process for the synthesis of ivabradine and addition salts thereof with a pharmaceutically acceptable acid

摘要

603483 Disclosed herein is a preparation of (P1) ivabradine (I) involving a reductive amination reaction of 4-(7,8-dimethoxy-2-oxo-1,2,4,5-tetrahydro-benzo[d]azepin-3-yl)-butyraldehyde (V) with ((S)-3,4-dimethoxy-bicyclo[4.2.0]octa-1(6),2,4-trien-7-ylmethyl)-methyl-amine (VI) in the presence of an iron-based catalyst (VII), optionally in the presence of trimethylamine N-oxide, under dihydrogen pressure of 1-20 bars, in an organic solvent or mixture of organic solvents, at 25-100°C