PROCESS FOR THE PREPARATION OF 1,3-DIHYDRO-2H-3-BENZAZEPIN-2-ONE AND APPLICATION TO THE PREPARATION OF IVABRADINE AND THEIR PHARMACEUTICALLY ACCEPTABLE SALTS

摘要

Method for preparing an N-substituted dihydro-3-benzazepine derivative (I) comprises reacting the corresponding N-unsubstituted compound (IV) with an alkylating agent (V). Method for preparing an N-substituted dihydro-3-benzazepine derivative of formula (I) comprises reacting the corresponding N-unsubstituted compound of formula (IV) with an alkylating agent (V) of formula X-CH 2CH 2CHR 1R 2, in an organic solvent and in presence of base (sodium or potassium hydroxides, aqueous ammonia or a (hydrogen)carbonate). R 1 and R 21-6C linear or branched alkoxy or together complete a 1,3-dioxan or 1,3-dioxolan ring; X = halo, preferably bromo, tosylate, mesylate or triflate Independent claims are also included for the following: (1) (I) as new compounds when R 1 and R 2 together complete a 1,3-dioxan or 1,3-dioxolan ring; and (2) method for synthesis of ivabradine or its pharmaceutically acceptable salts from (I). [Image].