NOVEL PROCESS FOR THE SYNTHESIS OF 7,8-DIMETHOXY-1,3-DIHYDRO-2H-3-BENZAZEPIN-2-ONE AND THE APPLICATION TO THE SYNTHESIS OF IVABRADINE AND ITS SALTS OF ADDITION TO A PHARMACEUTICALLY ACCEPTABLE ACID

摘要

Preparation of 7,8-dimethoxy-1,3-dihydro-2H-3-benzazepin-2-one (I), comprises (a) transforming (3,4-dimethoxyphenyl)acetic acid (IV) into an amide compound (V), and (b) subjecting (V) to a cyclization reaction in an acidic condition to give (I), after isolating. Preparation of 7,8-dimethoxy-1,3-dihydro-2H-3-benzazepin-2-one (I), comprises (a) transforming (3,4-dimethoxyphenyl)acetic acid (IV) into an amide compound of formula (V), and (b) subjecting (V) to a cyclization reaction in an acidic condition to give (I), after isolating. Either R 1, R 2 : 1-6C alkoxy; or CR 1R 2 : 1,3-dioxane, 1,3-dioxolane or 1,3-dioxepane. An independent claim is included for a preparation of ivabradine and its salts, comprising transforming (IV) into (I), then transforming (I) into ivabradine and optionally converting ivabradine into its addition salt using an acid comprising hydrochloric acid, hydrobromic acid, sulfuric acid, phosphoric acid, acetic acid, trifluoroacetic acid, lactic acid, pyruvic acid, malonic acid, succinic acid, glutaric acid, fumaric acid, tartaric acid, maleic acid, citric acid, ascorbic acid, oxalic acid, methanesulfonic acid, benzenesulfonic acid or camphoric acid, and their hydrates. [Image] ACTIVITY : Cardiant; Vasotropic; Antianginal; Antiarrhythmic. MECHANISM OF ACTION : None given.