An efficient and impurity-free process for telmisartan: An antihypertensive drug

Organic Process Research and Development

Volumn 11, Issue 1, 2007, Pages 81-85

  Reddy, Kikkuru Srirami ^a   Srinivasan, Neti ^a   Reddy, Chinta Raveendra ^a   Kolla, Naveenkumar ^a   Anjaneyulu, Yerremilli ^b   Venkatraman, Sundaram ^a   Bhattacharya, Apurba ^a   Mathad, Vijayavitthal T ^a  

^a DR REDDY'S LABORATORIES LTD   (India)

^b JAWAHARLAL NEHRU TECHNOLOGICAL UNIVERSITY   (India)

Author keywords

[No Author keywords available]

Indexed keywords

EID: 33847703808     PISSN: 10836160     EISSN: None     Source Type: Journal    
DOI: 10.1021/op060200g     Document Type: Article

References (13)

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2. (b) Norbert, H.; Berthold, N.; Uwe, R.; Jacobus, C. A.; Van, M.; Wolfgang, W.; Michael, E. U.S. Patent 5,591,762, 1997.
3. (c) Ruth, R. W.; William, J. C.; John, D. I.; Michael, R. C.; Kristine, P.; Ronald, D. S.; Pieter, B. M. W. M. T. J. Med. Chem. 1996, 39 (3), 625-656.
4. http://www.rxlist.com/cgi/generic2/telmisartan.htm.
5. (a) Uwe, J. R.; Gerhard, B. N.; Kai, M. H.; Helmut, W.; Michael, E.; Jacobus, C. A.; Van, M.; Wolfgang, W.; Norbert, H. H. J. Med. Chem. 1993, 36, 4040-4051.
6. (b) Merlos, M.; Casas, A.; Castaner, J. Drugs Future 1997, 22 (10), 1112-1116.
7. Carini, D. J.; Dunicia, J. V. Eu. Patent 2,53,310, 1988.
8. Venkataraman, S.; Mathad, V. T.; Kikkuru, S. R.; Neti, S.; Chinta, R. R.; Arunagiri, M.; Routhu, L. K PCT WO 06/044754A2, 2006.
9. 2CO explored for monomethylation of 15, DMS was found to be superior to obtain 15.
10. Structures of these impurities were tentatively proposed based on MS-MS data and a probable reaction mechanism and then synthesized as shown in Scheme 3. These impurities were characterized by NMR, mass, and IR techniques and further confirmed to be present in the sample by HPLC coinjection and spiking methods (0.1%).
11. Shen, J.; Li, J.; Yan, T.; Li, H.; Ji, R. CN 1,344,712, 2002.
12. Several brominating agents such as molecular bromine, N-bromosuccinimide (NBS), and 1,3-dibromo-5,5-dimethylhydantoin (DBDMH) resulted in 13 along with the dibromo impurity 26. The formation of the dibromo impurity 26 is varying from 20-45% by HPLC. The content of 26 is nearly 45% in the case of NBS bromination, whereas the same is in the range of 15%-20% in the case of DBDMH. Hence, DMDBH has been utilized as the brominating agent in the process. However impurity 26 did not participated in the next step and was easily washed out to a nondetected level during the isolation of 14 in the condensation step.
13. Robert, E. D.; Peter, S.; Herbert, N.; Kenneth, S.; William, I. F. D. J. Pharm. Sci. 2000, 89 (11), 1465-1479.