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Study on the synthesis technology of anticancer drug Gilteritinib fumarate

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Abstract

Based on the reported routes, a convergent eight-step approach to Gilteritinib fumarate was designed, which is suitable for industrial implementation. The first key intermediate, 3,5-dichloro-6-ethylpyrazine-2-carboxamide (6), was obtained from 2,6-dichloropyrazine in 49.3% yield by two subsequent one-pot Minisci reactions. The second key intermediate, 1-methyl-4-(piperidin-4-yl)piperazine (3), was synthesized from Boc-4-piperidone and N-methylpiperazine in 88.5% overall yield via two step reaction sequence that included reductive amination and the removal of Boc protective group. The target compound, Gilteritinib fumarate, was obtained in five steps from 1-fluoro-2-methoxy-4-nitrobenzene in 46.9% overall yield. Of special interest in this reaction sequence is the Ullmann-type coupling that was performed in the presence of the CuI-l-quebrachitol catalytic system providing an excellent catalytic effect.

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References

  1. G. Todde, R. Friedman, Phys. Chem. Chem. Phys., 2019, 21, 18467–18476; DOI: https://doi.org/10.1039/c9cp02938a.

    Article  CAS  PubMed  Google Scholar 

  2. G. Todde, R. Friedman, J. Chem. Inf. Model., 2020, 60, 4005–4020; DOI: https://doi.org/10.1021/acs.jcim.0c00544.

    Article  CAS  PubMed  Google Scholar 

  3. E. D. Pulte, K. J. Norsworthy, Y. Wang, Q. Xu, H. Qosa, R. Gudi, D. Przepiorka, W. Fu, O. O. Okusanya, K. B. Goldberg, R. A. De Claro, A. T. Farrell, R. Pazdur, Clin. Cancer Res., 2021, 27, 3515; DOI: https://doi.org/10.1158/1078-0432.CCR-20-4271.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. C. M. McMahon, A. E. Perl, Expert Rev. Clin. Pharmacol., 2019, 12, 841; DOI: https://doi.org/10.1080/17512433.2019.1657009.

    Article  CAS  PubMed  Google Scholar 

  5. I. Shimada, K Kurosawa, T. Matsuya, K. Iikubo, Y. Kondoh, A. Kamikawa, H. Tomiyama, Y. Iwai, Pat. WO 2010128659A1, 2010.

  6. T. Akiba, H. Hoshii, I. Shimada, K. Komenoi, K. Nishikawa, Y. Morinaga, Pat. CN 107207468A, 2017.

  7. Q. Yue, Z. Zhou, Q. Gao, B. Zheng, Pat. CN 106083821A, 2016.

  8. Y. Chen, X. Zhuang, Pat. CN 111423387A, 2020.

  9. J. Dong, Y. Zhang, X. Li, X. Wang, Y. Zhuang, Pat. CN 112062728A, 2020.

  10. K. Nishimura, K. Takeo, K. I. Shimoda, T. Nishi, Pat. WO 2020,138,281 A1, 2020.

  11. L. Wu, X. Liu, C. Z. Ding, S. Chen, L. Hu, L. Zhao, W. Pan, G. Hu, J. Li, Pat. WO 2019,015,655, 2019.

  12. M. Fan, W. Zhou, Y. Jiang, D. Ma, Org Lett., 2015, 17, 5934; DOI: https://doi.org/10.1021/acs.orglett.5b03230.

    Article  CAS  PubMed  Google Scholar 

  13. F. Du, Q. Zhou, Y. Fu, Y. Chen, Y. Wu, G. Chen, Synlett, 2019, 30, 2161; DOI: https://doi.org/10.1055/s-0039-1690707.

    Article  CAS  Google Scholar 

  14. Y. Jiang, L. Xu, C. Zhou, D. Ma, in C-H and C-X Bond Functionalization: Transition Metal Mediation, Ed. X. Ribas, RSC Catalysis Series, RCS Publ., Cambridge, 2013, No. 11, p. 1.

    Google Scholar 

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Authors and Affiliations

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

    Huashen Xu, Lu Chen, Yuanguang Chen, Yang Fu, Feng Xu & Guoliang Chen

Authors
  1. Huashen Xu
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  2. Lu Chen
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  3. Yuanguang Chen
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  4. Yang Fu
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  5. Feng Xu
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  6. Guoliang Chen
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Corresponding author

Correspondence to Guoliang Chen.

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The authors declare no competing interests.

Additional information

This work was funded by the Liaoning Revitalization Talents Program (XLYC1908031), Basic Research Project of Department of Education of Liaoning Province — natural sciences (2020LJC02).

No human or animal subjects were used in this research.

Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, Vol. 72, No. 8, pp. 1921–1928, August, 2023.

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Xu, H., Chen, L., Chen, Y. et al. Study on the synthesis technology of anticancer drug Gilteritinib fumarate. Russ Chem Bull 72, 1921–1928 (2023). https://doi.org/10.1007/s11172-023-3977-9

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  • DOI: https://doi.org/10.1007/s11172-023-3977-9

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