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A novel synthesis of imatinib and its intermediates

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Abstract

A convenient method has been developed for the synthesis of imatinib and two of its intermediates. N-(2-Methyl-5-nitrophenyl)-4-(3-pyridyl)-2-pyrimidinamine, obtained from 2-(methylsulfonyl)-4-(3-pyridyl)pyrimidine via nucleophilic substitution, was reduced by N2H4·H2O/FeCl3·6H2O/C in 92% yield. The resulting amine was condensed with 4-[(4-methylpiperazin-1-yl)methyl]benzoic acid dihydrochloride, which was prepared from 4-(chloromethyl)benzonitrile via substitution and hydrolysis reactions, to provide the final product imatinib in good yield and high purity.

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References

  1. Druker B, Talpaz M, Resta DJ (2001) N Engl J Med 344:1031

    Article  CAS  Google Scholar 

  2. O’Brien SG, Guilhot F, Larson RA, Gathmann I, Baccarani M (2003) N Engl J Med 348:994

    Article  Google Scholar 

  3. Druker BJ, Guilhot F, O’Brien SG, Gathmann I, Kantarjian H (2006) N Engl J Med 355:2408

    Article  CAS  Google Scholar 

  4. Wang SH (2002) J Leukemia Lymphoma 11:29

    Google Scholar 

  5. Zimmermann J (1993) EP Patent 0564409

  6. Loiseleur D, Kaufmann D, Abel S (2003) WO Patent 2003066613

  7. Liu YF, Wang CL, Bai YJ, Han N, Jiao JP, Qi XL (2008) Org Process Res Dev 12:490

    Article  CAS  Google Scholar 

  8. Kompella A, Bhujanga Rao AKS, Venkaiah Chowdary N (2004) WO Patent 2004108699

  9. Szakacs Z, Beni S, Varga Z, Orfi L, Keri G, Noszal B (2005) J Med Chem 48:249

    Article  CAS  Google Scholar 

  10. Szczepek W, Luniewski W, Kaczmarek L, Zagrodzki B, Samson Lazinska D, Szele Jewski W (2006) WO Patent 2006071130

  11. Huang AL, Liu X, Lior Z, Joseph K (2006) US Patent 2006149061

  12. Tang CJ, Jia CC (2009) CN Patent 100451015

  13. Zimmermann J, Buchdunger E, Mett H (1996) Bioorg Med Chem Lett 6:1221

    Article  CAS  Google Scholar 

  14. Collins JM, Klecker JRW, Anderson LW (2003) US Patent 20030198594

  15. Kankan RN, Rao DR (2004) WO Patent 074502

  16. Leonett F, Capaldi C, Carotti A (2007) Tetrahedron Lett 48:3455

    Article  Google Scholar 

  17. Breaux EJ, Zwikelmaier KE (1981) J Heterocycl Chem 18:183

    Article  CAS  Google Scholar 

  18. Schenone P, Sansebastiano L, Mosti L (1990) J Heterocycl Chem 27:295

    Article  CAS  Google Scholar 

  19. Dorigo P, Fraccarollo D, Santostasi G, Maragno I, Floreani M, Borea PA, Mosti L, Sansebastiano L, Fossa P, Orsini F, Benetollo F, Bombieri G (1996) J Med Chem 39:3671

    Article  CAS  Google Scholar 

  20. Marchetti F, Sayle KL, Bently J, Clegg W (2007) Org Biomol Chem 5:1577

    Article  CAS  Google Scholar 

  21. Huang H, Hutta DA, Rinker JM, Hu H (2009) J Med Chem 52:1081

    Article  CAS  Google Scholar 

  22. Gayo LM, Suto MJ (1997) Tetrahedron Lett 38:211

    Article  CAS  Google Scholar 

  23. Grant KJ, Jon R, Andrew L, Christophe BB, Richard D, Lambert V (2007) WO Patent 2007085833

  24. Zhao LY, Curran PJ, Belanger DB, Hamann B, Reddy PA, Paruch K, Guzi TJ, Dwyer MP, Siddiquim A, Tadikonda PK (2007) WO Patent 2007058942

  25. Ruano JLG, Martinez MC, Rodriguez JH, Olefirowicz EM, Eliel EL (1992) J Org Chem 57:4215

    Article  Google Scholar 

  26. Spaltenstein A, Carpine PA, Miyake F, Hopkins PB (1987) J Org Chem 52:3759

    Article  CAS  Google Scholar 

  27. Watanabe M, Koike H, Ishiba T, Okada T, Seo S, Hirai K (1997) Bioorg Med Chem 5:437

    Article  CAS  Google Scholar 

  28. Fu RZ, Xu XX, Dang Q, Chen F, Bai X (2006) Org Lett 9:571

    Article  Google Scholar 

  29. Lotspeich FJ (1965) J Org Chem 30:2068

    Article  CAS  Google Scholar 

  30. Kim KS, Hwang HJ, Hahn CS (1989) Bull Korean Chem Soc 10:482

    CAS  Google Scholar 

  31. Webb KS (1994) Tetrahedron Lett 35:3457

    Article  CAS  Google Scholar 

  32. Ivanov AS, Shishkov SV (2009) Monatsh Chem 140:619

    Article  CAS  Google Scholar 

  33. Bornmann W, Alauddin M, Gelovani (2008) WO Patent 2008024829

  34. Kil KE, Ding YS, Lin KS, Alexoff D, Kim SW, Shea C, Xu YW, Muench L, Fowler JS (2007) Nucl Med Biol 34:153

    Article  CAS  Google Scholar 

  35. Sairam P, Puranik R, Kelkar AS, Sasikiran S, Veerender M, Parvathi A (2003) Synth Commun 33:3597

    Article  CAS  Google Scholar 

  36. Zimmermann J, Switzerland W (1996) US Patent 5521184

  37. Boully L, Darabantu M, Turck A, Plé N (2005) J Heterocycl Chem 42:1423

    Google Scholar 

Download references

Acknowledgments

We gratefully acknowledge the financial support from the Shanghai Science and Technology Mission (10ZR1409600) and the Program for New Century Excellent Talents in University (NCET). We also thank the Laboratory of Organic Functional Molecules, the Sino-French Institute of ECNU for support.

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Authors and Affiliations

  1. Department of Chemistry, Institute of Medicinal Chemistry, East China Normal University, Shanghai, 200062, People’s Republic of China

    Haiyan Liu, Wenpin Xia, Yu Luo & Wei Lu

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  1. Haiyan Liu
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  2. Wenpin Xia
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  3. Yu Luo
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  4. Wei Lu
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Correspondence to Wei Lu.

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Liu, H., Xia, W., Luo, Y. et al. A novel synthesis of imatinib and its intermediates. Monatsh Chem 141, 907–911 (2010). https://doi.org/10.1007/s00706-010-0334-0

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