Process Development of the RIPK1 Inhibitor Oditrasertib Part 1: Continuous Synthesis of the Pyridine Core

A three-step synthesis of the core of the investigational RIPK1 inhibitor oditrasertib (DNL788, SAR443820) is described. This route features a telescoped three-step sequence enabled by continuous flow and a single crystallization to isolate the target bromopyridine in 68% overall yield and excellent purity (greater than 99.5% by weight percent and LCAP). The telescoped continuous process showed significant improvements in efficiency compared with the prior batch manufacturing route.