Metal-Catalyzed C–N Bond Forming Reaction Selection and Process Development for the Manufacture of AZD7594

Process development activities required to develop a robust and scalable synthetic route to AZD7594 (1) are disclosed. Included in this paper is the rationale for the selection of a palladium-mediated Buchwald–Hartwig coupling to form a key C–N bond. Reaction optimization and understanding were performed to minimize impurity formation and to develop a robust control strategy. The optimized synthetic sequence was used to manufacture 220 kg of AZD7594 (1) for clinical trials.