Green chemistry in process research and development in pharmaceutical industry

Recently, green chemistry (GC) plays an important role for manufacturing active pharmaceutical ingredients (APIs) at pharmaceutical companies. For example, large amount of aluminum waste was originally involved and dichloromethane used as a solvent in the process of a new anticholinergic agent, Vamicamide (FK 176), useful for the treatment of urinary incontinence. Non-selective and tedious procedures for alkylation of quinazoline nucleons were used on a laboratory scale in the process of a novel aldose reductase inhibitor, Zenarestat (FK 366) developed for the remedy of diabetic complications. These problems must be excluded before realizing a truly efficient process on a large scale. New process involved much less amount of waste in the case of Vamicamide, and utilized regioselective alkylation reaction for Zenarestat. As a result, E-factor and reaction mass efficiency (RME) were dramatically improved. Herein, we report our efforts leading to an efficient, practical and environmentally friendly process amenable to a large scale synthesis.