Browse > Article
http://dx.doi.org/10.5012/jkcs.2010.54.4.447

Improvement of the Synthetic Route for Epinastine Antihistamine  

Baek, Du-Jong (Department of Chemistry, College of Natural Sciences, Sangmyung University)
Kim, Moon-Sik (Synthetic Research Lab, Charm Jo-A, Co. Ltd.)
Publication Information
Journal of the Korean Chemical Society / v.54, no.4, 2010 , pp. 447-450 More about this Journal
Abstract
In this study, the improved large-scale synthetic route for epinastine hydrochloride, the second-generation antihistamine, was developed. The original synthetic route involves the synthesis of an aminomethyl derivative, the main intermediate, and in this process hazardous materials such as very toxic phosgene and sodium cyanide along with the explosive and expensive aluminum chloride and lithium aluminum hydride were used. In order to improve the synthetic route, we developed industrially very useful process to prepare the aminomethyl intermediate by the synthesis of the phthalimidomethyl derivative first and easy removal of the phthalyl group using hydrochloric acid or methyl hydrazine, and hazardous materials and expensive reagents were excluded in this process.
Keywords
Epinastine hydrochloride; Antihistamine; Synthesis; Process development;
Citations & Related Records

Times Cited By SCOPUS : 0
연도 인용수 순위
  • Reference
1 Ikeda, S.; Takahashi, Y. Method for Preparing 6-Aminomethyl-6,11-dihydro-5H-dibenz[b,e]azepine. U. S. Patent 7,196,193 B2, Mar. 27, 2007.
2 Simmons, F. E. R.; Simmons, K. J. New Engl. J. Med. 1994, 330, 1663.   DOI
3 Grant, J. A.; Danielson, L.; Rihoux, J. P.; DeVos, C. A. Allergy 1999, 54, 700.   DOI
4 van Bever, H. P. Eur. J. Pediatr. 1992, 151, 870.   DOI
5 Amon, U.; Gibbs, B. F.; Buss, G.; Nitschke, M. Inflamm. Res. 2000, 49, 112.   DOI
6 Kamei, C.; Akagi, M.; Mio, M.; Kitazumi, K.; Izushi, K.; Masaki, S.; Tasaka, K. Immunopharm. Immunotoxicol. 1992, 14, 191.   DOI
7 Data from IMS Health Korea (2009).
8 Walther, G.; Schneider, C. S.; Weber, K.-H.; Fugner, A. Heterocyclic compounds, processes for their preparation and pharmaceutical compositions containing them. UK Patent Application GB 2,071,095, Sept. 16, 1981.
9 Walther, G.; Schneider, C. S.; Weber, K.-H.; Fugner, A. Fused Dibenzo Imidazolo Compounds, Compositions and Use. U. S. Patent 4,313,931, Feb. 2, 1982.
10 van der Burg, W. J.; Bonta, I. L.; Delobelle, J.; Ramon, C.; Vargaftig, B. J. Med. Chem. 1970, 13, 35.   DOI