Process for the preparation of aliskiren

摘要

The present invention provides a novel process and novel intermediates useful in the synthesis of pharmaceutically active compounds, especially renin inhibitors, such as Aliskiren, or a salt thereof, preferably Aliskiren hemifumarate.

主权项

1. A process for the preparation of Aliskiren hemifumarate of Formula I, comprising the steps of: (i) reducing the compound of Formula VIIA with or without isolation of intermediate of Formula VIIA-Int, to obtain the compound of Formula VIIA-amine, which can be optionally converted to acid-addition salt thereof; (ii) protecting the compound of Formula VITA-amine with a suitable protecting agent in the presence of a base to obtain the compound of Formula VIIA-N-PG, wherein PG is a protecting group selected from the group consisting of BOC, FMOC, substituted or unsubstituted Cbz and trityl; (iii) reacting the compound of Formula VITA-N-PG with compound of Formula C in presence of 2-hydroxy pyridine and base to obtain compound of the Formula X—N-PG wherein PG is a protecting group selected from the group consisting of BOC, FMOC, substituted or unsubstituted Cbz and trityl; (iv) deprotecting the compound of Formula X—N-PG with acid or base or catalytic hydrogenolysis using hydrogen gas or catalytic hydrogen transfer in presence of organic solvent to obtain Aliskiren of the Formula X (v) treating Aliskiren of the Formula X with fumaric acid to obtain Aliskiren hemifumarate of Formula I.