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An Improved Process for Preparation of Dabigatran Etexilate Mesylate
Corresponding Author(s) : D. Ramachandran
Asian Journal of Chemistry,
Vol. 29 No. 6 (2017): Vol 29 Issue 6
Abstract
An improved process for the preparation of dabigatran etexilate mesylate, wherein the process is substantially free to eliminates the potential impurities. The impurities are formed due to presence of contaminated starting ingredients that is present in commercially available n-hexyl chloro formate. The present invention is to control impurities by using pure n-hexanol in place of n-hexyl chloro formate. Over all yields is good and process can’t requires expensive catalysts. Dabigtran is used to prevent strokes in those with arterial fibrillation due to heart valve causes, as well as deep venous thrombosis (DVT). Moreover, the present invention is providing simple, industrial scalable and cost-effective process, which affords good quality and yield.
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- J. van Ryn, J. Stangier, S. Haertter, K.-H. Liesenfeld, W. Wienen, M. Feuring and A. Clemens, Thromb. Haemost., 103, 1116 (2010); https://doi.org/10.1160/TH09-11-0758.
- A.J. Awad, B.P. Walcott, C.J. Stapleton, V. Yanamadala, B.V. Nahed and J.-V. Coumans, Neurosurg Focus, 34, 1 (2013) https://doi.org/10.3171/2013.2.FOCUS1323.
- FDA Drug Safety Communication: (Dabigtran Etexilate Mesylate) should not be Used in Patients with Mechanical Prosthetic Heart Valves, U.S. Food and Drug Administration (FDA); Retrieved October 29, 2014.
- S.D. Dwivedi, R.C. Singh and J.M. Raval, Process for the Preparation of Dabigtan Etexilate Mesylate and Polymorophs of Intermediates Thereof, US Patent US2015/0011589 A1 (2015).
- N.H. Hauel, H. Nar, H. Priepke, U. Ries, J.-M. Stassen and W. Wienen, J. Med. Chem., 45, 1757 (2002); https://doi.org/10.1021/jm0109513.
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- M.J. Serra, L.E. Duran and L. Rao, Dabigtran Etexilate and Related Substances, Processes and Composition, and Use of the Substances as Reference Standards and Markers, WO Patent 2012152855A1 (2014).
- S. Sinare, S. Borhade, S. Jadhav, V. Acharya and P.V. Srinivasan, Int. J. Pharm. Res. Dev., 6, 119 (2014).
- N. Hauel, U. Ries, H. Priepke, W. Wienen and J. Stassen, Disubstituted Bicyclic Heterocycles, their Production and use as Medicaments, WO Patent 1998037075A1 (1998).
- V. Jayaraman, S. Patel, S. Mistry, M. Timbadiya and P. Tamboli, Novel Preference Markers of Dabigtran Etexilate, WO 2013024394A1 (2013).
- S.K. Singh, S.B. Bhirud, F.P. D'Souza, N.G. Jambukar, P. Thombre and A. Soni, Process for Dabigtran Etexilate and Intermediate Thereof, WO Patent 2014/041559 A3 (2014).
References
J. van Ryn, J. Stangier, S. Haertter, K.-H. Liesenfeld, W. Wienen, M. Feuring and A. Clemens, Thromb. Haemost., 103, 1116 (2010); https://doi.org/10.1160/TH09-11-0758.
A.J. Awad, B.P. Walcott, C.J. Stapleton, V. Yanamadala, B.V. Nahed and J.-V. Coumans, Neurosurg Focus, 34, 1 (2013) https://doi.org/10.3171/2013.2.FOCUS1323.
FDA Drug Safety Communication: (Dabigtran Etexilate Mesylate) should not be Used in Patients with Mechanical Prosthetic Heart Valves, U.S. Food and Drug Administration (FDA); Retrieved October 29, 2014.
S.D. Dwivedi, R.C. Singh and J.M. Raval, Process for the Preparation of Dabigtan Etexilate Mesylate and Polymorophs of Intermediates Thereof, US Patent US2015/0011589 A1 (2015).
N.H. Hauel, H. Nar, H. Priepke, U. Ries, J.-M. Stassen and W. Wienen, J. Med. Chem., 45, 1757 (2002); https://doi.org/10.1021/jm0109513.
T.J. Moore, M.R. Cohen and D.R. Mattison, BMJ, 349, g4517 (2014). https://doi.org/10.1136/bmj.g4517.
M.J. Serra, L.E. Duran and L. Rao, Dabigtran Etexilate and Related Substances, Processes and Composition, and Use of the Substances as Reference Standards and Markers, WO Patent 2012152855A1 (2014).
S. Sinare, S. Borhade, S. Jadhav, V. Acharya and P.V. Srinivasan, Int. J. Pharm. Res. Dev., 6, 119 (2014).
N. Hauel, U. Ries, H. Priepke, W. Wienen and J. Stassen, Disubstituted Bicyclic Heterocycles, their Production and use as Medicaments, WO Patent 1998037075A1 (1998).
V. Jayaraman, S. Patel, S. Mistry, M. Timbadiya and P. Tamboli, Novel Preference Markers of Dabigtran Etexilate, WO 2013024394A1 (2013).
S.K. Singh, S.B. Bhirud, F.P. D'Souza, N.G. Jambukar, P. Thombre and A. Soni, Process for Dabigtran Etexilate and Intermediate Thereof, WO Patent 2014/041559 A3 (2014).