Process Development of ONO-2506:  A Therapeutic Agent for Stroke and Alzheimer's Disease

Abstract

A process for the synthesis of ONO-2506, an agent that suppresses astrocyte activation, has been developed. Significant improvement of the level of impurities in the final product has been achieved compared with the laboratory-scale procedure. Kilogram quantities of the compound have been supplied for preclinical studies by this improved process, with both a high quality (99.8%) and a high optical purity (99.6% ee). This was achieved by formation of a crystalline salt of an intermediate which could be recrystallized to give high purity. Toward the future launch of this product, residual problems such as byproduct formation during stereoselective allylation and removal of chiral auxiliary steps were also solved by further investigation.