PROCESS FOR THE PREPARATION OF PYRIDO2,1-a ISOQUINOLINE DERIVATIVES BY CATALYTIC ASYMMETRIC HYDROGENATION OF AN ENAMINE

摘要

The invention relates to a process for the preparation of pyrido[2,1-a] isoquinoline derivatives of the formula; ;wherein R², R³ and R⁴ are as defined in the specification, comprising the steps of a) catalytic asymmetric hydrogenation of an enamine of the formula; ;wherein R¹ is lower alkyl, in the presence of a transition metal catalyst containing a chiral diphosphane ligand, b) introduction of an amino protecting group Prot and c) amidation of the ester to form an amide of formula; ;wherein R², R³, R⁴ and Prot are as defined in the specification.