Synthetic process of antitumor drug dacomitinib

This paper describes a practical process for the preparation of antitumor drug dacomitinib. It was synthesized by eleven steps from 2-amino-4-fluorobenzoic acid by cyclization, nitration, halogenation, coupling and reduction reactions with the total yield of 36. 1% and one-step yield of 75%-90 %. The intermediates and target compound were characterized by NMR and MS. This practical synthetic process of dacomitinib highlights comparable yield, low-cost, optimized condition and easier purification.