Bulletin of the Korean Chemical Society

Korean Chemical Society (대한화학회)
권호 표지
DOI QR코드

DOI QR Code

An Improved Convergent Approach for Synthesis of Erlotinib, a Tyrosine Kinase Inhibitor, via a Ring Closure Reaction of Phenyl Benzamidine Intermediate

  • Asgari, Davoud (Research Center for Pharmaceutical Nanotechnology, Faculty of Pharmacy, Tabriz University of Medical Sciences) ;
  • Aghanejad, Ayuob (Drug Applied Research Center, Tabriz University of Medical Sciences) ;
  • Mojarrad, Javid Shahbazi (Department of Medicinal Chemistry, Faculty of Pharmacy, Tabriz University of Medical Sciences)
  • Received : 2010.11.29
  • Accepted : 2011.01.10
  • Published : 2011.03.20
Download PDF
~1A' System of CHBr" href="/article/JAKO201112261546909.view?orgId=anpor"> ⟨ Previous Next ⟩

Abstract

An improved convergent and economical method has been developed for the synthesis of erlotinib, a 4-anilinoquinazoline and an EGFR-tyrosine kinase inhibitor for treatment of non-small-cell lung cancer. The final two steps for the formation of this 4-anilinoquinazoline from suitable 2-aminobenzonitrile intermediate and 3-ethynylaniline were modified and were performed in a simple one-pot reaction. The ring-closing mechanism for the formation of erlotinib from the suitable formamidine intermediate and 3-ethynylaniline was investigated and determined to proceed via the formation of phenyl benzamidine intermediate rather than involving Dimroth rearrangement reported earlier. The new benzamidine intermediate was isolated for the first time and characterized.

Keywords

References

  1. El-Rayes, B. M.; LoRusso, P. M. British Journal of Cancer 2004,91, 418. https://doi.org/10.1038/sj.bjc.6601921
  2. Arteaga, C. L. J. Clin. Oncol. 2001, 19, 32s.
  3. Bianco, R.; Gelardi, T.; Damiano, V.; Ciardiello, F.; Tortora, G. J. Targ. Oncol. 2007, 2, 31. https://doi.org/10.1007/s11523-006-0038-x
  4. Krause, D. S.; Van Etten, R. A. Engl. J. Med. Chem. 2005, 353,172. https://doi.org/10.1056/NEJMra044389
  5. Huang, S.; Armstrong, E. A.; Benavente, S.; Chinnaiyan, P.; Harari,P. M. Cancer. Res. 2004, 64, 5355. https://doi.org/10.1158/0008-5472.CAN-04-0562
  6. Gridelli, G.; Bareschino, M. A.; Schettino, C.; Rossi, A.; Maione,P.; Ciardiello, F. J. Oncologist. 2007, 12, 840. https://doi.org/10.1634/theoncologist.12-7-840
  7. Brahimi, F.; Matheson, S. L.; Dudouit, F.; Mcnamee, J. P.; Tari, A.M.; Jean-Claude, B. J. J. Pharm. Exp. Ther. 2002, 303, 238. https://doi.org/10.1124/jpet.102.039099
  8. Townsley, C. A.; Major, P.; Siu, L. L.; Dancey, J.; Chen, E.; Pond,G. R.; Nicklee, T.; Ho, J.; Hedley, D.; Tsao, M.; Moore, M. J.;Oza, A. M. British Journal of Cancer 2006, 94, 1136. https://doi.org/10.1038/sj.bjc.6603055
  9. Lu, Y. Y.; Jing, D. D.; Xu, M.; Wu, K.; Wang, X. P. World J. Gastroenterol. 2008, 14, 5403. https://doi.org/10.3748/wjg.14.5403
  10. Festuccia, C.; Gravina, G. L.; Biordi, L.; Ascenzo, S.; Dolo, V.;Ficorella, C.; Ricevuto, E.; Tombolini, V. J. The Prostate. 2009,69, 1529. https://doi.org/10.1002/pros.20995
  11. Yamasaki, F.; Zhang, D.; Bartholomeusz, C.; Sudo, T.; Hortobagyi,G.; Kurisu, K.; Ueno, N. T. J. Mol. Cancer. Ther. 2007, 6, 2168. https://doi.org/10.1158/1535-7163.MCT-06-0514
  12. Vasey, P. A.; Gore, M.; Wilson, R.; Rustin, G.; Gabra, H.; Guastalla,J. P.; Lauraine, E. P.; Paul, J.; Carty, K.; Kaye, S. Brit. J. Cancer2008, 98, 1774. https://doi.org/10.1038/sj.bjc.6604371
  13. Barker, A.; J. EP 0 566 226 (1993).
  14. Schnur, R. C.; Arnold, L. D. U.S. Patent 5 747 498 (1998).
  15. Knesl, P.; Röseling, D.; Jordis, U. Molecules 2006, 11, 286. https://doi.org/10.3390/11040286
  16. Chandregowda, V.; Rao, G. V.; Reddy, G. C. Org. Proc. Res. Dev.2007, 11(5), 813. https://doi.org/10.1021/op700054p
  17. Kangani, C. O.; Day, B. W.; Kelley, D. E. Tetrahedron Lett. 2007,48, 5933. https://doi.org/10.1016/j.tetlet.2007.06.119
  18. Telvekar, V. N.; Rane, R. A. Tetrahedron Lett. 2007, 48, 6051. https://doi.org/10.1016/j.tetlet.2007.06.108
  19. Gilday, J. P.; Welham, M. J. PCT Int Appl. WO 023783 (2005).
  20. Chandregowda, V.; Rao, G. V.; Reddy, G. C. Heterocycles 2007,71(1), 39. https://doi.org/10.3987/COM-06-10884

Cited by

  1. ChemInform Abstract: An Improved Convergent Approach for Synthesis of Erlotinib (IV), a Tyrosine Kinase Inhibitor, via a Ring Closure Reaction of Phenyl Benzamidine Intermediate. vol.42, pp.31, 2011, https://doi.org/10.1002/chin.201131155
  2. The Development of a Dimroth Rearrangement Route to AZD8931 vol.21, pp.3, 2017, https://doi.org/10.1021/acs.oprd.6b00412
  3. Synthesis, characterization, crystal structure, Hirshfeld interaction and bio-evaluation studies of 4-amino quinazoline sulfonamide derivatives vol.1167, pp.None, 2011, https://doi.org/10.1016/j.molstruc.2018.04.055
  4. Globally Approved EGFR Inhibitors: Insights into Their Syntheses, Target Kinases, Biological Activities, Receptor Interactions, and Metabolism vol.26, pp.21, 2011, https://doi.org/10.3390/molecules26216677
  5. Targeted combined therapy in 2D and 3D cultured MCF-7 cells using metformin and erlotinib-loaded mesoporous silica magnetic nanoparticles vol.38, pp.7, 2011, https://doi.org/10.1080/02652048.2021.1979672
  6. Recent advances and trends in nanoparticles based photothermal and photodynamic therapy vol.37, pp.None, 2011, https://doi.org/10.1016/j.pdpdt.2021.102697