An Effective and Convenient Process for the Preparation of Ticagrelor: Optimized by Response Surface Methodology and One-Pot Reaction

Abstract

An effective and convenient process for the preparation of ticagrelor (1), an antiplatelet drug, has been developed. The synthesis of 1 is a four-step reaction. Each reaction step was optimized individually to develop a scalable and industrial friendly process. The critical step to prepare intermediate 5 was optimized using the response surface methodology. One-pot reaction was used to telescope the next three steps, resulting in 75% overall yield in comparison to the initial 63% yield obtained from the stepwise isolation process. The feasibility and consistency of the improved process was verified by pilot-scale test.