Perifosine, KRX-0401, NKA17, D-21266
哌立福新Chemical Name: N,N-Dimethylpiperidinium-4-yl(octadecyl)phosphate; 1,1-Dimethyl-4-[[(octadecyloxy)hydroxyphosphoryl]oxy]piperidinium inner salt
CAS No. 157716-52-4
项目整合开发状态: Phase II
项目研究机构: Keryx (Proprietary), Asta Medica (Originator), Zentaris (Originator), Access Pharmaceuticals (Licensee), National Cancer Institute (Codevelopment), Nippon Kayaku (Codevelopment)
合成路线:Perifosine was synthesized via a two-step process.In the first step,phosphorus oxytrichloride (I) was reacted with 4-hydroxy-1-methylpiperidine hydrochloride (II) in dichloromethane at room temperature using pyridine as auxiliary base.The resulting intermediate,without isolation,was reacted with octadecanol (III) to yield desmethyl perifosine (IV).Desmethyl perifosine was purified by recrystallization prior to methylation.The second step consisted of the methylation of desmethyl perifosine (IV),which was carried out with p-toluenesulfonic acid methyl ester in boiling ethanol using potassium carbonate as base.The crude perifosine solution that was obtained after filtration of the cooled reaction mixture was treated with ion exchange resin in order to remove remaining salts and ionic by-products.Pure perifosine was obtained after evaporation and crystallization.
📌 参考资料/链接：
参考文献标题:Perifosine
文献作者:Engel,J.; Hilgard,P.; Nsner,G.; Voss,V.; Traiser,M.; Klenner,T.; Kutscher,B.
参考来源:Drugs Fut 2000,25(12),1257
📄 详细内容
合成路线:Perifosine was synthesized via a two-step process.In the first step,phosphorus oxytrichloride (I) was reacted with 4-hydroxy-1-methylpiperidine hydrochloride (II) in dichloromethane at room temperature using pyridine as auxiliary base.The resulting intermediate,without isolation,was reacted with octadecanol (III) to yield desmethyl perifosine (IV).Desmethyl perifosine was purified by recrystallization prior to methylation.The second step consisted of the methylation of desmethyl perifosine (IV),which was carried out with p-toluenesulfonic acid methyl ester in boiling ethanol using potassium carbonate as base.The crude perifosine solution that was obtained after filtration of the cooled reaction mixture was treated with ion exchange resin in order to remove remaining salts and ionic by-products.Pure perifosine was obtained after evaporation and crystallization.
参考文献标题:Synthesis of hexadecylphosphocholine (miltefosine).Alkylphophocholines: New drugs in cancer therapy
文献作者:Eibl,H.; Engel,J.
参考来源:Prog Exp Tumor Res 1992,341-5
产品链接: CAS No. 157716-52-4››