Chemistry of Heterocyclic Compounds

, Volume 54, Issue 6, pp 638–642 | Cite as

An improved synthesis of 4-chloro-7H-pyrrolo[2,3-d]pyrimidine

  • Yu-Liu Zhang
  • Cheng-Tao Xu
  • Ting Liu
  • Yong Zhu
  • Yu LuoEmail author

An improved seven-step synthesis of 4-chloro-7H-pyrrolo[2,3-d]pyrimidine from dimethyl malonate with 31% overall yield is described. The procedure is operationally simple and practical for the synthesis of the 4-chloro-7H-pyrrolo[2,3-d]pyrimidine building block.


pyrimidine Janus kinase inhibitor ozonolysis synthesis 


This research was financially supported by The National Key Technology R&D Program (No. 2015BAK45B00). We also thank the Laboratory of Organic Functional Molecules, the Sino-French Institute of ECNU for support.

Supplementary material

10593_2018_2320_MOESM1_ESM.pdf (1.9 mb)
ESM 1 (PDF 1918 kb)


  1. 1.
    Aaronson, D. S.; Horvath, C. M. Science 2002, 296, 1653.CrossRefPubMedGoogle Scholar
  2. 2.
    (a) Laurence, A.; Pesu, M.; Silvennoinen, O.; O'Shea, J. Open Rheumatol. J. 2012, 6, 232. (b) O'Shea, J.; Holland, S. M.; Staudt, L. M. N. Engl. J. Med. 2013, 368, 161.Google Scholar
  3. 3.
    Verstovsek, S.; Mesa. R. A.; Gotlib, J.; Levy, R. S.; Gupta, V.; DiPirso, J. F.; Catalano, J. V.; Deininger, M.; Miller, C.; Silver, R. T.; Talpaz, M.; Winton, E. F.; Harvey, J. H.; Arcasoy, M. O.; Hexner, E.; Lyons, R. M.; Paquette, R.; Raza, A.; Vaddi, K.; Erickson-Viitanen, S.; Koumenis, I. L.; Sun, W.; Sandor, V.; Kantarjian, H. M. N. Engl. J. Med. 2012, 366, 799.Google Scholar
  4. 4.
    Wang, A. X.; Liu, B. N.; Liu, Y.; Liu, D. K.; Liu, M. Drug Eval. Res. 2014, 37, 169.Google Scholar
  5. 5.
    Gonzales, A. J.; Bowman, J. W.; Fici, G. J.; Zhang, M.; Mann, D. W.; Mitton-Fry, M. J. Vet. Pharmacol. Ther. 2014, 37, 317.CrossRefPubMedPubMedCentralGoogle Scholar
  6. 6.
    O'Shea, J. J.; Kontzias, A.; Yamaoka, K.; Tanaka, Y.; Laurence, A. Ann. Rheum. Dis. 2013, 72, 111.CrossRefGoogle Scholar
  7. 7.
    Gras, J. Drugs Future 2014, 39. 547.Google Scholar
  8. 8.
    Ma, L.; Clayton, J. R.; Walgren, R. A.; Zhao, B.; Evans, R. J.; Smith, M. C.; Heinz-Taheny, K. M.; Kreklau, E. L.; Bloem, L.; Pitou, C.; Shen, W.; Strelow, J. M.; Halstead, C.; Rempala, M. E.; Parthasarathy, S.; Gillig, J. R.; Heinz, L. J.; Pei, H.; Wang, Y.; Stancato, L. F.; Dowless, M. S.; Iversen, P. W.; Burkholder, T. P. Blood Cancer J. 2013, 3, 109.CrossRefGoogle Scholar
  9. 9.
    Taylor, E. C.; Patel, H. H. US Patent 5254687; Chem Abstr. 1994, 120, 164207.Google Scholar
  10. 10.
    Furneaux, R. H.; Tyler, P. C. J. Org. Chem. 1999, 64, 8411.CrossRefPubMedGoogle Scholar
  11. 11.
    Cheung, M.; Harris, P. A.; Lackey, K. E. Tetrahedron Lett. 2001, 42, 999.CrossRefGoogle Scholar
  12. 12.
    Davoll, J. J. Chem. Soc. 1960, 131.Google Scholar
  13. 13.
    Liu, P.-L.; Wang, D.-J.; Wu, Y.-Z.; Cao, G.-F.; Xia, M. US Patent 9714233; Chem Abstr. 2014, 161, 459988.Google Scholar
  14. 14.
    Hao, B.-Y.; Chen, X.-Z.; Zhang, W.-H. Chin. J. Org. Chem. 2010, 30, 918.Google Scholar
  15. 15.
    Melik-Ogandzhanyan, R. G.; Gapoyan, A. S.; Khachatryan, V. É.; Mirzoyan, V. S. Chem. Heterocycl. Compd. 1982, 18, 1305. [Khim. Geterotsikl. Soedin. 1982, 1686.]Google Scholar
  16. 16.
    Zhan, L.; You, D. L.; Wu, Y. Q.; Xu, Y. N.; Luo, Y. CN Patent 107011347; Chem. Abstr. 2017, 167, 368362.Google Scholar
  17. 17.
    Andrews, M. D.; Bagal, S. K.; Gibson, K. R.; Omoto, K.; Ryckmans, T.; Skerratt, S. E.; Stupple, P. A. WO Patent 2012137089; Chem. Abstr. 2012, 157, 606000.Google Scholar
  18. 18.
    Sokolova, V. N.; Magidson, O. Yu. Chem. Heterocycl. Compd. 1968, 4, 385. [Khim. Geterotsikl. Soedin. 1968, 519.]Google Scholar
  19. 19.
    Boros, E. E.; Thompson, J. B.; Katamreddy, S. R.; Carpenter, A. J. J. Org. Chem. 2009, 74, 3587.CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  • Yu-Liu Zhang
    • 1
  • Cheng-Tao Xu
    • 1
  • Ting Liu
    • 1
  • Yong Zhu
    • 2
  • Yu Luo
    • 1
    Email author
  1. 1.Shanghai Engineering Research Center of Molecular Therapeutics and New Drug Development, School of Chemistry and Molecular EngineeringEast China Normal UniversityShanghaiP. R. China
  2. 2.Suzhou Highfine Biotech Co., Ltd.SuzhouP. R. China

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