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A mild protocol for the synthesis of N-methyltransferase G9a inhibitor BIX-01294

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Abstract

A synthetic route to BIX-01294 was designed by means of retrosynthetic analysis and convergent synthesis. Using 2-amino-4,5-dimethoxybenzoic acid and urea as the starting materials, BIX-01294 was synthesized in the four following steps: cyclization, chlorination and two steps of ammonolysis. In contrast to the previously described approaches to BIX-01294, our final step conditions do not require microwave irradiation, utilize cheap and simple methanesulfonic acid as a catalyst to promote the synthesis of the target BIX-01294 under mild conditions (PrnOH, reflux, 5 h) in 75.5% yield. The overall yield of BIX-01294 over four steps was 26.4%.

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Authors and Affiliations

  1. Key Laboratory of Structure-Based Drug Design & Discovery of Ministry of Education, Shenyang Pharmaceutical University, 110016, Shenyang, People’s Republic of China

    Yajie Shi, Yuanguang Chen, Lu Chen, Jianwen Sun & Guoliang Chen

Authors
  1. Yajie Shi
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  2. Yuanguang Chen
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  3. Lu Chen
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  4. Jianwen Sun
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  5. Guoliang Chen
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Corresponding author

Correspondence to Guoliang Chen.

Additional information

This work was funded by the Liaoning Revitalization Talents Program (XLYC1908031, China), Major Basic Research Project of Natural Science Foundation of Shandong Province (ZR2018ZC1056, China), Taishan Industry Leading Talents Project (NO: 2018TSCYCX-17).

No human or animal subjects were used in this research.

The authors declare no competing interests.

Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 11, pp. 2489–2494, November, 2022.

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Shi, Y., Chen, Y., Chen, L. et al. A mild protocol for the synthesis of N-methyltransferase G9a inhibitor BIX-01294. Russ Chem Bull 71, 2489–2494 (2022). https://doi.org/10.1007/s11172-022-3678-9

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  • DOI: https://doi.org/10.1007/s11172-022-3678-9

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