Synthesis and analytical characterization of the dasatinib API

Dasatinib (DAS) 1 is a thiazole-based ATP-competitive, dual Src/Abl kinase inhibitor used as targeted therapy medication in the treatment of patients with chronic myelogenous leukemia and acute lymphoblastic leukemia.¹ Even two decades after the discovery of 1, the available synthetic routes still present significant potential for improvement.² Given its pharmacological importance and highly functionalized chemical structure, the synthesis of this active pharmaceutical ingredient remains both attractive and challenging. In this work, we report the synthesis of dasatinib through a four-step linear route starting from 3-ethoxyacrylic acid, with particular emphasis on studying amide bond formation in the DAS structure via a mixed carbonic anhydride strategy, an approach not yet reported in the literature. DAS was obtained in 19% overall yield with a purity of 99.909%. Analytical characterization by PXRD, TGA, DSC, and thermomicroscopy indicates the crystallinity of DAS; however, it may be associated with a mixture of solid forms.