ISSN print edition: 0366-6352 ISSN electronic edition: 1336-9075 Registr. No.: MK SR 9/7 Published monthly

Improved protocol for synthesis of N-(3-chloro-4-fluorophenyl)-7-methoxy-6-(3-morpholin-4-ylpropoxy) quinazolin-4-amine (gefitinib)

Pawan Kumar, Muhammad Taufiq F. Mazlee, Muhammad K. Abdul Wahab, Chandra Kant Belwal, Ramesh Kumar, and Shahnawaz Sajid

Oncogen Pharma Sdn Bhd, Shah Alam, Malaysia

E-mail: pawan.kumar@oncogenpharma.com

Abstract: An improved three-step process for the synthesis of gefitinib from readily available starting material is discussed in this protocol. The protocol is based on the synthesis, isolation, characterization of novel intermediates and their application in the alkylation step for the synthesis of gefitinib. Excellent results were achieved over the conventional synthetic methodologies. Isolation of these intermediates were effective in replacing high boiling solvent with low boiling solvent(s) but also in eliminating base from the reaction. These conditions led to effective elimination of all the prior art reported impurities. This high-yielding process is cost-effective with isolable and stable intermediates. These intermediates were characterized using NMR, mass spectroscopy, DSC and XRPD analyses.

Keywords: Gefitinib ; Iressa ; Alkali metal salts ; O-Alkylation ; Novel intermediate ; Improved protocol 

Full paper is available at www.springerlink.com.

DOI: 10.1007/s11696-018-0564-x

Chemical Papers 73 (1) 39–46 (2019)