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

  • MOLECULAR-BIOLOGICAL PROBLEMS OF DRUG DESIGN AND MECHANISM OF DRUG ACTION
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Pharmaceutical Chemistry Journal Aims and scope

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.

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Acknowledgments

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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Authors and Affiliations

  1. Department of Pharmaceutical Engineering, Qingdao University of Science & Technology, 53 Zhengzhou Road, Qingdao, Shandong province, 266000, China

    Li-hong Wang & Jun-hong Liu

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  1. Li-hong Wang
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  2. Jun-hong Liu
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Correspondence to Li-hong Wang.

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Wang, Lh., Liu, Jh. An Effective and Convenient Process for the Preparation of Ticagrelor: Optimized by Response Surface Methodology and One-Pot Reaction. Pharm Chem J 52, 813–819 (2019). https://doi.org/10.1007/s11094-019-1906-x

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  • DOI: https://doi.org/10.1007/s11094-019-1906-x

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