New Synthesis of 7-(3-chloropropoxy)-4-hydroxy-6-methoxyquinoline-3-carbonitrile, a Key Intermediate to Bosutinib

Article abstract of DOI:10.1002/jhet.2811

A new and convenient synthesis of 7-(3-chloropropoxy)-4-hydroxy-6-methoxyquinoline-3-carbonitrile, the key intermediate to bosutinib, is described on a hectogram scale. 5-Bromo-2-methoxyphenol is adopted as the starting material via the simple chemical process including Friedel-Crafts reaction, alkylation, bromination, cyano substitution, and so on to give the 3-amino-2-(2-bromobenzoyl)acrylonitrile compound 25, which underwent key intramolecular cyclization at K₂CO₃/DMF condition; the title product was obtained in 36.9% yield over 7 steps and 98.71% purity (HPLC).