Download PDF
Synthesis 2020; 52(02): 273-280
DOI: 10.1055/s-0039-1690248
paper
© Georg Thieme Verlag Stuttgart · New York

A Concise and Efficient Approach to 2,6-Disubstituted 4-Fluoro­pyrimidines from α-CF3 Aryl Ketones

Fangran Liu
a   Department of Chemistry, Shanghai University, 99 Shang Da Road, Shanghai 200444, P. R. of China   Email: qianqun@shu.edu.cn
b   State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 555 Zu Chong Zhi Road, Shanghai 201203, P. R. of China   Email: chyang@simm.ac.cn
,
Xiaofei Zhang
b   State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 555 Zu Chong Zhi Road, Shanghai 201203, P. R. of China   Email: chyang@simm.ac.cn
,
Qun Qian∗
a   Department of Chemistry, Shanghai University, 99 Shang Da Road, Shanghai 200444, P. R. of China   Email: qianqun@shu.edu.cn
,
Chunhao Yang  ∗
b   State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 555 Zu Chong Zhi Road, Shanghai 201203, P. R. of China   Email: chyang@simm.ac.cn
› Author AffiliationsThis study was financially supported by the National Natural Science Foundation of China (81872722), Science and Technology Commission of Shanghai Municipality (18431907100), Shanghai Sailing Program (17YF1423400), and SKLDR/Shanghai Institute of Materia Medica (SIMM) (SIMM1601ZZ-03).
Further Information

Publication History

Received: 30 August 2019

Accepted after revision: 21 October 2019

Publication Date:
06 November 2019 (online)

    Permissions and Reprints All articles of this category


Abstract

Herein, a concise and efficient protocol to synthesize a series of 2,6-disubstituted 4-fluoropyrimidines as universal and useful building blocks in medicinal chemistry is reported. From readily accessible α-CF3 aryl ketones and different amidine hydrochlorides, this method provides a very practical approach to this kind of compounds under mild conditions with good to excellent yields.

Key words

fluoropyrimidine - α-CF3 aryl ketone - metal-free - mild conditions

Supporting Information

    Supporting information for this article is available online at https://doi.org/10.1055/s-0039-1690248.
  • Supporting Information
 

  • References

  • 1 Isanbor C, O’Hagan D. J. Fluorine Chem. 2006; 127: 303
    Crossref
  • 2 Joshi G, Nayyar H, Kalra S, Sharma P, Munshi A, Singh S, Kumar R. Chem. Biol. Drug Des. 2017; 90: 995
    CrossrefPubMed
  • 3 Fang Z, Zheng S, Chan K.-F, Yuan W, Guo Q, Wu W, Lui H.-K, Lu Y, Leung Y.-C, Chan T.-H, Wong K.-Y, Sun N. Eur. J. Med. Chem. 2019; 161: 141
    CrossrefPubMed
  • 4 Ghith A, Youssef KM, Ismail NS. M, Abouzid KA. M. Bioorg. Chem. 2019; 83: 111
    CrossrefPubMed
  • 5 Bai S, Liu S, Zhu Y, Wu Q. Tetrahedron Lett. 2018; 59: 3179
    Crossref
  • 6 Hagmann WK. J. Med. Chem. 2008; 51: 4359
    CrossrefPubMed
  • 7 Utz JP. N. Engl. J. Med. 1972; 286: 777
    CrossrefPubMed
  • 8 Saravolatz LD, Johnson LB, Kauffman CA. Clin. Infect. Dis. 2003; 36: 630
    CrossrefPubMed
  • 9 Goetz MP, Toi M, Campone M, Sohn J, Paluch-Shimon S, Huober J, Park IH, Trédan O, Chen S.-C, Manso L, Freedman OC, Garnica Jaliffe G, Forrester T, Frenzel M, Barriga S, Smith IC, Bourayou N, Di Leo A. J. Clin. Oncol. 2017; 35: 3638
    CrossrefPubMed
  • 10 Friedberg JW, Sharman J, Sweetenham J, Johnston PB, Vose JM, LaCasce A, Schaefer-Cutillo J, De Vos S, Sinha R, Leonard JP, Cripe LD, Gregory SA, Sterba MP, Lowe AM, Levy R, Shipp MA. Blood 2010; 115: 2578
    CrossrefPubMed
  • 11 deBoer GJ, Thornburgh S, Ehr RJ. Pest Manage. Sci. 2006; 62: 316
    CrossrefPubMed
  • 12 Zhang C, Zhou T, Wang J, Zhang S, Zhu L, Du Z, Wang J. Sci. Total Environ. 2018; 610-611: 769
    CrossrefPubMed
  • 13 Banks RE, Prakash A, Venayak ND. J. Fluorine Chem. 1980; 16: 325
    Crossref
  • 14 O’Neill MJ, Riesebeck T, Cornella J. Angew. Chem. Int. Ed. 2018; 57: 9103
    CrossrefPubMed
  • 15 Parks EL, Sandford G, Yufit DS, Howard JA. K, Christopher JA, Miller DD. Tetrahedron 2010; 66: 6195
    Crossref
  • 16 Nencka R, Votruba I, Hrebabecky H, Jansa P, Tloust’ova E, Horska K, Masojidkova M, Holy A. J. Med. Chem. 2007; 50: 6016
    CrossrefPubMed
  • 17 Wadsworth H, Jones PA, Chau WF, Durrant C, Morisson-Iveson V, Passmore J, O’Shea D, Wynn D, Khan I, Black A, Avory M, Trigg W. Bioorg. Med. Chem. Lett. 2012; 22: 5795
    CrossrefPubMed
  • 18 Bella M, Kobbelgaard S, Jørgensen KA. J. Am. Chem. Soc. 2005; 127: 3670
    CrossrefPubMed
  • 19 Kuduk SD, Di Marco CN, Chang RK, Ray WJ, Ma L, Wittmann M, Seager MA, Koeplinger KA, Thompson CD, Hartman GD, Bilodeau MT. Bioorg. Med. Chem. Lett. 2010; 20: 2533
    CrossrefPubMed
  • 20 Maes W, Van Rossom W, Van Hecke K, Van Meervelt L, Dehaen W. Org. Lett. 2006; 8: 4161
    CrossrefPubMed
    • 21a Klauke E, Oehlmann L, Baasner B. J. Fluorine Chem. 1982; 21: 495
      Crossref
    • 21b Bennett BK, Harrison RG, Richmond TG. J. Am. Chem. Soc. 1994; 116: 11165
      Crossref
  • 22 Inouye Y, Higuchi Y. J. Fluorine Chem. 1985; 27: 231
    Crossref
  • 23 Sedenkova KN, Averina EB, Grishin YK, Kuznetsova TS, Zefirov NS. Tetrahedron Lett. 2014; 55: 483
    Crossref
  • 24 Neumann CN, Hooker JM, Ritter T. Nature 2016; 534: 369
  • 25 Sather AC, Lee HG, De La Rosa VY, Yang Y, Müller P, Buchwald SL. J. Am. Chem. Soc. 2015; 137: 13433
    CrossrefPubMed
  • 26 Jiang B, Zhang X, Yang C. Org. Chem. Front. 2018; 5: 1724
    Crossref
  • 27 Shipe WD, Sharik SS, Barrow JC, McGaughey GB, Theberge CR, Uslaner JM, Yan Y, Renger JJ, Smith SM, Coleman PJ, Cox CD. J. Med. Chem. 2015; 58: 7888
    CrossrefPubMed
  • 28 Wu YB, Lu GP, Yuan T, Xu ZB, Wan L, Cai C. Chem. Commun. 2016; 52: 13668
    CrossrefPubMed