异环磷酰胺有关物质的合成  

Synthesis of related substance from ifosfamide

作　　者：付晖[1] 田金龙[2] 李新鹏[2] 吴松[2] 贾娴[1] 

机构地区：[1]沈阳药科大学制药工程学院,辽宁沈阳110016 [2]中国医学科学院北京协和医学院药物研究所天然药物活性物质与功能国家重点实验室卫生部天然药物生物合成重点实验室,北京100050

出　　处：《中国药物化学杂志》2015年第5期386-388,共3页Chinese Journal of Medicinal Chemistry

基　　金：石药集团心脑血管药物创新综合平台建设项目(2013ZX09402103)

摘　　要：目的合成异环磷酰胺原料药中的一种有关物质。方法以3-氨基丙醇为原料,与三氯氧磷环合制得2-氯-1-氧杂-3-氮杂-2-磷杂环己烷-2-氧化物(3);以1-氨基-2-丙醇为原料,与氯化亚砜反应制得2-氯丙胺盐酸盐(5);化合物3与5经取代、酰化、还原得到有关物质3-(2-氯乙基)-2-[(2-氯丙基)氨基]-1-氧杂-3-氮杂-2-磷杂环己烷-2-氧化物。结果与结论合成了异环磷酰胺原料药中的一种有关物质,其结构经1H-NM R、13C-NM R和M S谱确证,纯度在99%以上。该有关物质可作为异环磷酰胺原料药质量控制的对照品。In order to better perform the quality control of ifosfamide,the content determination of related substance 3-（ 2-chloroethyl）-[（ 2-chloropropyl） amino]tetrahydro-2H-1,3,2-oxazaphosphorine-2-oxide（ 1）w as required according to the standard comparison method in the Chinese Pharmacopeia（ CP）. Therefore,the related substance 1 w as intended to prepare in this paper. A new route w as designed to synthesize the target compound using 3-aminopropanol and 2-chloropropyl-1-amine hydrochloride as starting material. This new route w as successfully implemented to give the related substance 1 by reduction of the crucial intermediate 3-（ 2-chloroacetyl）-[（ 2-chloropropyl） amino]tetrahydro-2H-1,3,2-oxazaphosphorine-2-oxide using borane in a total yield of 24. 2%. The related substance 1 from ifosfamide w as verified by1H-NM R,13C-NM R and M S. Its purity w as over 99% by the detection of HPLC,and it could be used as the reference substance in the quality control of ifosfamide.

关 键 词：异环磷酰胺 有关物质 合成 

分 类 号：R914[医药卫生—药物化学]