A NEW AND PRACTICAL SYNTHESIS OF BOSUTINIB

摘要

New and improved synthetic route of bosutinib is described on a decagram scale. An intramolecular cyclization of 3-amino-2-(2-bromobenzoyl)-acrylonitrile (22) in K2CO3/DMF condition to form the key 3-cyano-4-hydroxyquinoline intermediate (13) is adopted as the key step. Bosutinib is obtained in 13.7% yield over ten steps and 98.9% purity (HPLC), which make it as a process of cost effective, environmentally friendly and feasible for scale-up operation.