Development of an Early Phase Process for a Potent Oligodendrocyte Precursor Cell Differentiator

Herein are described improvements in a discovery synthesis to enable a rapid scale up of 1 to support early phase clinical trials and formulation development studies. Process modifications included route redesign, simplifying a Mitsunobu reaction product's isolation, improving yields and impurity profiles for isolated intermediates, and removal of a chromatographic purification. Particle engineering studies identified a recrystallization protocol to produce 1 with enhanced solid-state properties. This improved process was scaled up to generate multikilogram quantities of drug substance with >99.8% area purity.