NEW PROCESS FOR THE PREPARATION OF FUNCTIONALISED BENZOCYCLOBUTENES, AND APPLICATION IN THE SYNTHESIS OF IVABRADINE AND ADDITION SALTS THEREOF WITH A PHARMACEUTICALLY ACCEPTABLE ACID.

摘要

A method for preparing the compounds of formula (IV): in which R1, R2, R3 and R4, which may be identical or different, are each a hydrogen atom, a linear or branched (C1-C6) alkyl group, a linear or branched (C1-C6) alkoxy group, a fluorine or chlorine atom, a protected amino group, a protected hydroxyl group, an alkoxycarbonyl group in which the alkoxy group is linear or branched (C1-C6), or a CF3 group, or R1=R4=H and R2 and R3 form, together with the carbon atoms which bear them, a 1,3 dioxolane group, R5 is a saturated or unsaturated, linear or branched (C1-C6) alkyl group, a linear or branched (C1-C6) hydroxyalkyl group in which the hydroxyl function is protected, or a CO2R7 group in which R7 is a linear or branched (C1-C6) alkyl group, and R6 is a cyano group or a CO2R8 group in which R8 is a linear or branched (C1-C6) alkyl group. Use in the synthesis of ivabradine, of addition salts thereof with a pharmaceutically acceptable acid, and of hydrates thereof.