Metal-Free Electrochemical Reduction of Nitroquinazoline Derivatives towards Synthesis of Afatinib and Dacomitinib

Abstract

This research offers a reduction process for the nitro group via the electrochemical method as a step in the synthesis of anticancer drugs afatinib and dacomitinib. This methodology provides wide substrate coverage and exhibits functional group tolerance using carbon electrodes. This synthetic approach offers several advantages: (1) metal-free reaction conditions, (2) absence of activated carbon, thus no filtration required in the work up process, (3) ambient-temperature reaction conditions, and (4) shorter reaction time. Moreover, this procedure is tolerant to a diverse range of anilino and alkoxy derivatives at the C-4 and C-7 positions of the quinazoline ring, yielding satisfactory product yields (33%–88%).