New process for the synthesis of (2e)-3-(3,4-dimethoxyphenyl)prop-2-enenitrile, and application in the synthesis of ivabradine and addition salts thereof with a pharmaceutically acceptable acid
GONZALEZ JOSE LORENZO,SANCHEZ FREDERIC,CARRANZA MARIA DEL PILAR,GARCIA ARANDA MARIA ISABEL
申请号：
NZ61676813
公开号：
NZ616768A
申请日:
2013.10.17
申请国别(地区):
NZ
年份:
2015
代理人:
摘要：
Disclosed is a process for the synthesis of 3,4-dimethoxy-cinnamonitrile / (2E)-3-(3,4-dimethoxyphenyl)prop-2-enenitrile as represented by the compound of formula (I), characterised in that 4-bromo-1,2-dimethoxybenzene of formula (IX) is subjected to a coupling reaction with acrylonitrile in an organic solvent, in the presence of: i) a palladium catalyst (such as palladium(II) acetate, palladium on carbon, and palladium(II) chloride)； ii) a ligand such as triphenylphosphine or tri(o-tolyl)phosphine； iii) a base such as triethylamine, sodium acetate, sodium carbonate or potassium carbonate； and iv) a phase transfer agent such as tetrabutylammonium bromide or tetrabutylammonium chloride. Also disclosed is the use of 3,4-dimethoxy-cinnamonitrile obtained by the above method, in the synthesis of ivabradine, and pharmaceutically acceptable salts thereof.
