NEW SYNTHETIC METHOD FOR (1S)-4,5-DIMETHOXY-1-(METHYLAMINOMETHYL)BENZOCYCLOBUTANE AND ITS ADDUCT SALT AND ITS APPLICATION TO SYNTHESIS OF IVABRADINE AND ITS ADDUCT SALT WITH PHARMACEUTICALLY ACCEPTABLE ACID

摘要

PPROBLEM TO BE SOLVED: To provide a synthetic method for a compound expressed with formula (I) and provide the application of the compound to the synthesis of ivabradine and its adduct salt with a pharmaceutically acceptable acid and their hydrates. PSOLUTION: The nitrile given by formula (III) is reduced with hydrogen and the resultant racemic amine is optically divided by using N-acetyl glutamic acid as an optical resolution agent to obtain (S) configuration optically active compound. Then, the compound is treated with a chloroformate to prepare a carbamate, which is reduced with a reducing agent to give the compound of formula (I). PCOPYRIGHT: (C)2006,JPO&NCIPI