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DOI: 10.1055/s-0040-1707267
Expedient Approach to the Synthesis of Betrixaban
C.R.R. is grateful to the Council of Scientific and Industrial Research (CSIR), New Delhi for financial support as part of mission mode project (INPROTICS; HCP 011).
Abstract
A new scalable route to synthesize the factor Xa (FXa) inhibitor betrixaban is disclosed. The product is obtained in a seven-step reaction sequence (in five stages using two one-pot reactions) starting from easily accessible 4-(N,N-dimethylcarbamimidoyl)benzoate. Effective isolation of intermediates, use of cost-effective amide formation and 2-methyltetrahydrofuran as an effective reaction solvent as well as for extraction in three of the stages, are key features. The strategy provides the desired product in 38% overall yield with high purity (>98%).
Supporting Information
- Supporting information for this article is available online at https://doi.org/10.1055/s-0040-1707267.
- Supporting Information
Publication History
Received: 29 July 2020
Accepted after revision: 17 August 2020
Article published online:
04 September 2020
© 2020. The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial-License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/)
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References
- 1 Eriksson BI, Quinlan DJ, Weitz JI. Clin. Pharmacokinet. 2009; 48: 1
- 2 Turpie AG. G, Bauce KA, Davidson BL, Fisher WD, Gent M, Huo MH, Sinha U, Gretler DD. Thromb. Haemost. 2009; 101: 68
- 3 Palladino M, Merli G, Thomson L. Expert Opin. Invest. Drugs 2013; 22: 1465
- 4 Zhang P, Huang W, Wang L, Bao L, Jia ZJ, Bauer SM, Goldman EA, Probst GD, Song Y, Su T, Fan J, Wu Y, Li W, Woolfrey J, Sinha U, Wong PW, Edwards ST, Arfsten AE, Clizbe LA, Kanter J, Pandey A, Park G, Hutchaleelaha A, Lambing JL, Hollenbach SJ, Scarborough RM, Zhu B.-Y. Bioorg. Med. Chem. Lett. 2009; 19: 2179
- 5 Huisman MV, Klok FA. Eur. Heart J. Suppl. 2018; 20: E12
- 6 Kanter JP, Suizno K, Zuberi SS. PCT Int. Appl. WO2008057972, 2008
- 7 Pandey A, Leitao EP. T, Rato J, Song ZJ. PCT application WO 2011084519, 2011
- 8 Li J, Chen L, Yan X, Li Y, Wei D, Wang D. J. Chem. Res. 2015; 39: 524
- 9 Pinto DJ, Qiao JX, Gangor T, Lam PY. S, Li Y.-L. PCT Int. Appl. WO2004083174, 2004 ; A2 20040930, 2004
- 10 Bailey C, Baker E, Hayler J, Kane P. Tetrahedron Lett. 1999; 40: 4847
- 11 Chen H, Xu X, Liu L, Tang G, Zhao Y. RSC Adv. 2013; 3: 16247
- 12 Errede LA, McBrady JJ. J. Org. Chem. 1977; 42: 3863