An environmentally responsible new route for the manufacture of sitagliptin has been achieved through scientific innovation. This work was recently recognized by winning the ICHEME Astra-Zeneca Award for Excellence in Green Chemistry. An NDA for sitagliptin was filed in December, 2005, as a new treatment for type II diabetes.

A first generation process, which used existing methodology to synthesize sitagliptin, was used to prepare over 100 kg of material and with modifications would have been a viable manufacturing process. However, in order to develop a highly efficient process for the preparation of sitagliptin, Merck researchers discovered a completely unprecedented transformation, the asymmetric catalytic hydrogenation of unprotected enamines. This new method provides a general solution to the synthesis of beta-amino acids; a class of molecules well known for their interesting biological properties. Merck scientists and engineers have applied this new method in a completely novel way, using it in the final step of synthesis, which maximizes the efficiency of the new route. This strategy is broadly applicable to other pharmaceutical targets and has been applied to the synthesis of several exploratory Merck drug substances. Implementation of the new route on manufacturing scale has led to over an 80 % reduction in the amount of waste produced and elimination of aqueous waste streams. The technology discovered, developed and implemented by Merck for the manufacture of sitagliptin is an excellent example of innovation resulting in benefits to the environment.