Copyright (c) 2013 AJC
This work is licensed under a Creative Commons Attribution 4.0 International License.
Research and Development of a Novel Process for Nilotinib: A Bcr-Abl Inhibitor
Corresponding Author(s) : K. Amala
Asian Journal of Chemistry,
Vol. 25 No. 8 (2013): Vol 25 Issue 8
Abstract
In this study, an efficient, economic and novel process for the production of highly pure nilotinib (1), a Bcr-Abl inhibitor in described. The synthesis comprises the chlorination of 4-methyl-3-nitro benzoic acid (2) to get 4-methyl-3-nitro benzoyl chloride (2A). Condensation of compound (2) with 5-(4-methyl-1H-imidazol-1-yl)-3-(trifluoromethyl)-benzeneamine (11) to obtain 4-methyl-N-[3-(4-methyl-1H-imidazol-1-yl-5-(trifluoromethyl)phenyl]-3-nitro-benzamide hydrochloride (3). Reducing compound (3) with stannous chloride (or) raney nickel to obtain 4-methyl-N-[3-(4-methyl-1H-imidazol-1-yl-5-(trifluoromethyl)phenyl]-3-amino-benzamide (4). Reaction of compound (4) with cyanamide to obtain 4-methyl-N-[3-(4-methyl-1H-imidazol-1-yl-5-(trifluoromethyl)phenyl]-3-guanidino-benzamide (5). Condensation of the compound (5) with 3-dimethylamino-1-(3-pyridyl)-2-propen-1-one (8) to obtain nilotinib (1).
Keywords
Download Citation
Endnote/Zotero/Mendeley (RIS)BibTeX
- T. O'Hare, D.K. Walters, M.W.N. Deininger and B.J. Druker, Cancer Cell, 7, 117 (2005).
- E. Weisberg, P.W. Manley, W. Breitenstein, J. Bruggen, S.W. CowanJacob, A. Ray, B. Huntly, D. Fabbro, G. Fendrich, E. Hall-Meyers, A.L. Kung, J. Mestan, G.Q. Daley, L. Callahan, L. Catley, C. Cavazza, M. Azam, D. Neuberg, R.D. Wright, D.G. Gilliland and J.D. Griffin, Cancer Cell, 7, 129 (2005).
- B. Werner, F. Pascal, J. Sandra and M.P. William, CAS No. 140: P77161v, WO 2004/005281 (2004).
- M. Joseph and S. Wen-Chung, CAS No. 146:81883, WO2006/135641 (2006).
- Y. Wang, V.K. Kansal, J. Zhu, R. Lifshitz-Liron, D.K.N. Mistry, S.I. Vasoya, S. Ariyamuthu and G. Pilarski, CAS No. 152:192145, US 2010/0016590 (2010).
- A. Stephen,A. Murat, E.R.B. Bernard, K. Chrostoph, S. Joseph, M. Mark, P. Mahavir, S. Wen-chung and X. Song, WO2006/135640 (2006).
References
T. O'Hare, D.K. Walters, M.W.N. Deininger and B.J. Druker, Cancer Cell, 7, 117 (2005).
E. Weisberg, P.W. Manley, W. Breitenstein, J. Bruggen, S.W. CowanJacob, A. Ray, B. Huntly, D. Fabbro, G. Fendrich, E. Hall-Meyers, A.L. Kung, J. Mestan, G.Q. Daley, L. Callahan, L. Catley, C. Cavazza, M. Azam, D. Neuberg, R.D. Wright, D.G. Gilliland and J.D. Griffin, Cancer Cell, 7, 129 (2005).
B. Werner, F. Pascal, J. Sandra and M.P. William, CAS No. 140: P77161v, WO 2004/005281 (2004).
M. Joseph and S. Wen-Chung, CAS No. 146:81883, WO2006/135641 (2006).
Y. Wang, V.K. Kansal, J. Zhu, R. Lifshitz-Liron, D.K.N. Mistry, S.I. Vasoya, S. Ariyamuthu and G. Pilarski, CAS No. 152:192145, US 2010/0016590 (2010).
A. Stephen,A. Murat, E.R.B. Bernard, K. Chrostoph, S. Joseph, M. Mark, P. Mahavir, S. Wen-chung and X. Song, WO2006/135640 (2006).