Improved Synthesis of Gefitinib and Erlotinib Hydrochloride‐ Anticancer Agents

Abstract

A highly efficient and commercially viable process for the synthesis of 6,7‐dihydroxy‐4‐anilinoquinazoline derivatives gefitinib (1) and erlotinib hydrochloride (2), used for the treatment of non‐small cell lung cancer (NSCLC) and pancreatic cancer, is reported. This new process has improved yields and avoids the unstable 4‐chloroquinazoline intermediate. The intermediates and final products were characterized by ¹H and ¹³C nuclear magnetic resonance (NMR), mass spectra (MS), and elemental analysis, and purities of final products were determined by high performance liquid chromatogram (HPLC) and potentiometric titration methods.

Keywords:

• erlotinib
• gefitinib
• methylthio quinazolines
• nonsmall cell lung cancer
• tyrosine kinase inhibitors (TKIs)

Acknowledgment

Our sincere thanks are due to Anil Kush, CEO, Vittal Mallya Scientific Research Foundation, for his keen interest and support in this work.