An Effective and Convenient Process for the Preparation of Ticagrelor: Optimized by Response Surface Methodology and One-Pot Reaction
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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.
Keywordsticagrelor synthesis process optimization response surface methodology one-pot reaction pilot-scale test
This work was supported by the National Natural Science Foundation of China (Grant No. 21546004) and Major National Science and Technology Projects (Grant No. 2014ZX09102043-001).
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