Development of an Efficient Manufacturing Process for E2212 toward Rapid Clinical Introduction
Minetaka Isomura, Taiju Nakamura, Atsushi Kamada, Takeo Sasaki, Toshiyuki Uemura, Yorihisa Hoshino, Masaaki Matsuda, Yongbo Hu, Daiju Hasegawa, Kazato Inanaga, Nobuaki Sato, Kazuhiro Yoshizawa, George A. Moniz, Gordon D. Wilkie, Francis G. Fang, Yoshihiro Nishikawa, Katsuya Tagami · Organic Process Research & Development · 2019
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.