PROCESS FOR THE PREPARATION OF PYRIDO[2,1-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 (I), weherein R², R³ and R⁴ are as defined in the specification, comprising the steps of: a) catalytic asymmetric hydrogenation of an enamine of the formula (II), 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 (V), wherein R², R³, R⁴ and Prot are as defined in the specification.