Abstract
A highly efficient continuous synthesis has been developed for telmisartan, the active ingredient in the antihypertensive drug, Micardis. This synthetic route employs a convergent strategy that requires no intermediate purifications or solvent exchanges. The key step in the reaction scheme is a Suzuki cross-coupling reaction between two functionalized benzimi-dazoles that is catalyzed by a solid-supported Pd catalyst. This flow-based approach utilizes a tubular reactor system coupled with a plug flow packed bed cartridge unit that produces telmisartan in an 81% isolated yield.
Article PDF
Similar content being viewed by others
References
Lim, S. S.; Vos, T.; Flaxman, A. D.; Danaei, G.; Shibuya, K.; Adair-Rohani, H. et al. Lancet 2012, 380, 2224–2260.
Wienen, W.; Hauel, N.; Van Meel, J. C. A.; Narr, B.; Ries, U.; Entzeroth, M. Br. J. Pharmacol. 1993, 110, 245–252
Battershill, A. J.; Scott, L. J. Drugs 2006, 66, 51–83
McClellan, K. J.; Markham, A. Drugs 1998, 56, 1039–1044.
Cernes, R.; Mashavi, M.; Zimlichman, R. Vasc. Health Risk Manag. 2011, 7, 749–75.
Burnier, M.; Brunner, H. R. Lancet 2000, 355, 637–645.
Benson, S. C.; Pershadsingh, H. A.; Ho, C. I.; Chittiboyina, A.; Desai, P.; Pravenec, M.; Qi, N.; Wang, J.; Avery, M. A.; Kurtz, T. W. Hypertension 2004, 43, 993–1002
Benndorf, R. A.; Rudolph, T.; Appel, D.; Schwedhelm, E.; Maas, R.; Schulze, F.; Silberhorn, E.; Boger, R. H. Metab. Clin. Exp. 2006, 55, 1159–1164
Mann, J. F. E.; Schmieder, R. E.; McQueen, M.; Dyal, L.; Schumacher, H.; Pogue, J.; Wang, X.; Maggioni, A.; Budaj, A.; Chaithiraphan, S.; Dickstein, K.; Keltai, M.; Metasärinne, K.; Oto, A.; Parkhomenko, A.; Piegas, L. S.; Svendsen, T. L.; Teo, K. K.; Yusuf, S. Lancet 2008, 372, 547–553.
Mogi, M.; Li, JM.; Tsukuda, K.; Iwanami, J.; Min, LJ.; Sakata, A.; Fujita T.; Iai, M; Horiuchi, M. Biochem Biophys. Res. Commun. 2008, 375,(3), 446–449.
Ries, U. J.; Mihm, G.; Narr, B.; Hasselbach, K. M.; Wittneben, H.; Entzeroth, M.; Van Meel, J. C. A.; Wienen, W.; Hauel, N. H. J. Med. Chem. 1993, 36, 4040–4051
Reddy, K. S.; Srinivasan, N.; Reddy, C. R.; Kolla, N.; Anjaneyulu, Y.; Venkatraman, S.; Bhattacharya, A.; Mathad, V. T. Org. Proc. Res. Dev. 2007, 11, 81–85
Goosen, L. J.; Knauben, T. J. Org. Chem. 2008, 73, 8631–8634
Kumar, A. S.; Ghosh, S.; Mehta, G. N. Beilstein J. Org. Chem. 2010, 6, 25.
Martin, A. D.; Siamaki, A. R.; Belecki, K.; Gupton, B. F. J. Org. Chem. 2015, 80, 1915–1919.
Wang, P.; Zheng, G.; Wang, Y.; Wang, X.; Wei, H.; Xiang, W. Tetrahedron 2012, 68, 2509–2512.
Molander, G. A.; Trice, S. L. J.; Dreher, S. D. J. Am. Chem. Soc. 2010, 132, (50), 17701–17703.
Author information
Authors and Affiliations
Corresponding authors
Rights and permissions
About this article
Cite this article
Martin, A.D., Siamaki, A.R., Belecki, K. et al. A Flow-Based Synthesis of Telmisartan. J Flow Chem 5, 145–147 (2015). https://doi.org/10.1556/JFC-D-15-00002
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1556/JFC-D-15-00002