药物化学  >> Vol. 2 No. 1 (February 2014)

盐酸西那卡塞的合成工艺研究
Synthesis Process of Cinacalcet Hydrochloride

DOI: 10.12677/HJMCe.2014.21001, PDF, HTML,  被引量 下载: 2,911  浏览: 11,645 

作者: 卞学国:南京医工医药有限公司,南京;王均伟:南京医工医药有限公司,南京;中国药科大学药物化学教研室,南京;朱启华, 徐云根:中国药科大学药物化学教研室,南京

关键词: 盐酸西那卡塞合成工艺研究Cinacalcet Hydrochloride; Synthesis; Process Research

摘要: 目的:确定一条适合工业化生产的盐酸西那卡塞的合成工艺。方法:以1-萘乙酮为起始原料,经Leuckart- Wallch反应、水解、手性拆分、缩合、还原、成盐6步反应合成盐酸西那卡塞。结果:通过工艺改进,简化了操作过程,提高了安全性,降低了生产成本,总收率14.38%(此合成路线总收率未经文献报道),纯度99.9%。结论:本方法条件温和,操作简单,成本低,收率高,适合大规模生产。
Abstract: Objective: In order to get a suitable process of cinacalcet hydrochloride for industrial production. Methods: Cinacalcet hydrochloride was synthesized from 1-acetonaphthone via six steps, including Leuckart-Wallch reaction, hydrolysis, chiral resolution, condensation, reduction and finally salification. Results: Through improvement, we simplified the operations, improved the safety of the process and reduced the costs. The overall yield was 14.38% (The overall yield of this synthetic route was unreported) with a purity of 99.9%. Conclusion: This synthetic process is of mild conditions, easy operation, low cost and high yield, and is suitable for large-scale production.

文章引用: 卞学国, 王均伟, 朱启华, 徐云根. 盐酸西那卡塞的合成工艺研究[J]. 药物化学, 2014, 2(1): 1-5. http://dx.doi.org/10.12677/HJMCe.2014.21001

参考文献

[1] Nemeth, E.F., Heaton, W.H., Miller, M., et al. (2004) Pharmacodyna-micsof the type II calcimimetic compounds cinacalcet HCl. Journal of Pharmacology and Experimental Therapeutics, 2, 627-635.
[2] Van, W.B.C., Moe, S.T., Balandrin, M.F., et al. (2001) Calciumrecep-tor-active compounds: US, 6211244. 2001-04-03.
[3] Sorbera, L.A., Castaner, R.M. and Bayes, M. (2002) Cinacalcethydrochloride: Treatment of hyperparathyroidism. Drugs of Future, 27, 831-836.
[4] Lifshitz-Liron, R., Eisenstadt, A., Wizel, S., et al. (2006) Process for preparing of cinacalcet hydrochloride: WO2006125026.
[5] Arava, V.R., Gorentla, L. and Dubey, P.K. (2012) A novel asymmetric synthesis of cinacalcethydrochloride. Beilstein Journal of Organic Chemistry, 1, 1366-1373.
[6] Bernard, C., Larsen, R., Martinelli, M.J., et al. (2012) Methods of synthesizing cinacalcet and salts thereof: US8183415.
[7] Shinde, G.B., Niphade, N.C., Deshmukh, S.P., et al. (2011) Industrial application of the forster reaction: Novel one-pot synthesis of cinacalcet hydrochloride, a calci-mimetic agent. Organic Process Research & Development, 15, 455-461.
[8] Lifshitz-Liron, R. (2007) Process for the prepartion of cinacalcet base: WO2007127445.
[9] Thiel, O.R., Bernard, C., Tor-mos, W., et al. (2008) Practical synthesis of the calcimimetic agent cinacalcet. Tetrahedron Letters, 49, 13-15.
[10] Bijukumar, G., Ma-loyesh, B., Bhaskar, B.S., et al. (2008) Efficient synthesis of cinacalcet hydrochloride. Synthetic Communications, 38, 1512-1517.
[11] Stan-dard Commodity Classification No. of Japan 873999 (2010)
[12] Blacker, A. and Martin, J. (2004) Process for the prepara-tion of aromatic amines: WO2004110976.
[13] 倪发根 (2011) 一种(R)-1-(1-萘基)乙胺的化学酶拆分制备方法:CN102277392.
[14] Hu, C.C. and Chen, Y.H. (2012) Preparation method of cinacalcet and pharmaceutical salts thereof: WO2012051737.