An Improved Procedure for the Preparation of Poziotinib

Abstract

Abstract-1. Objective: To improve the synthetic procedure of the anticancer drug poziotinib. 2. Methods: The poziotinib was synthesized in six stages starting from 7-methoxy-4-oxo-3,4-dihydroquinazolin-yl acetate (2) by chlorinated, ammonification, hydrolysis, condensation, take off Boc and amidation reaction. Compound 2 reacted with POCl3 followed by ammonification to afford 8. Compound 8 reacted with ammonia water in methanol to obtain 9 which passes through the condensation reaction to obtain 6. Compound 6 took off Boc in the CF3COOH followed by amidation reaction to afford the poziotinib. Results: The anticancer drug poziotinib was synthesized by using 7-methoxy-4-oxo-3,4-dihydroquinazolin-yl acetate as starting material in 6 steps. The structures were characterized by 1H NMR and ESI-MS. 4. Conclusion: The starting material is very easy to get, the reaction conditions are moderate and the operation is convenient. The reaction steps are shortened and the overall yield is 37.2 %. This method is suitable for industrial producing.