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A practical synthesis for the key intermediate of apixaban

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Abstract

Apixaban is a highly potent, selective, and efficacious inhibitor of blood coagulation factor Xa. A practical and efficient process has been developed for the preparation of the key intermediate of apixaban. Starting from inexpensive 4-chloronitrobenzene and piperidine, an eight-step procedure for the intermediate has been developed. In this case, sodium chlorite is used twice to oxidize the piperidine cycle to the corresponding lactam under a CO2 atmosphere, resulting in the construction of two lactams. Furthermore, most of these reactions are highly efficient and practical as they occur under mild conditions. Most of the intermediates can be obtained through simple slurry or recrystallization, and column chromatography purification is not necessary.

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Acknowledgements

This work was supported by the National Natural Science Foundation of China (21372081, 21172072).

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Authors and Affiliations

  1. Engineering Research Centre of Pharmaceutical Process Chemistry, Ministry of Education, Shanghai Key Laboratory of New Drug Design, School of Pharmacy, East China University of Science and Technology, 130 Meilong Road, Shanghai, 200237, China

    Wenwen Dong, Tengfei Gong, Chaoyang Liu, Jia Lin & Changhu Chu

  2. Seasons Biotechnology (Taizhou) Co., Ltd., 21 Jiutiao Road, Jiaojiang District, Taizhou, 318000, Zhejiang, China

    Qiang Jia

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  1. Wenwen Dong
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  2. Tengfei Gong
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  3. Chaoyang Liu
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  4. Jia Lin
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  5. Qiang Jia
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  6. Changhu Chu
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Correspondence to Changhu Chu.

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Dong, W., Gong, T., Liu, C. et al. A practical synthesis for the key intermediate of apixaban. Monatsh Chem 155, 99–104 (2024). https://doi.org/10.1007/s00706-023-03143-7

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