Development of the telescoped flow Pd-catalyzed aerobic alcohol oxidation/reductive amination sequence in the synthesis of new phosphatidylinositide 3-kinase inhibitor (CPL302415)

Herein, we describe a two-step sequential flow synthesis: Pd-catalyzed aerobic oxidation to an aldehyde 2, which is then converted by reductive amination in H-Cube® PRO into CPL302415 (3). CPL302415 is our new PI3Kδ inhibitor, which is now under evaluation for the treatment of systemic lupus erythematosus. The process was optimized using the DoE approach and generalized to other biologically active derivatives of CPL302415.