Development of an Efficient Manufacturing Process for E2212 toward Rapid Clinical Introduction

Process studies of E2212 (1) toward rapid clinical introduction are described. Through comprehensive route-finding studies and optimization of key condensation and cyclization steps, a racemate-based manufacturing route was established and successfully scaled-up to the hundred kilogram scale. For the rapid delivery of a drug substance containing the Z isomer for preclinical safety studies, the successful scale-up of the photoisomerization of an olefin in a flow system is also presented.