Glufosfamide, glc-IPM, D-19575

葡磷酰胺Chemical Name: N,N'-Bis(2-chloroethyl)phosphorodiamidic acid beta-D-glucopyranosyl ester
CAS No. 132682-98-5
项目整合开发状态: Phase III
项目研究机构: Baxter Oncology (Originator), Threshold Pharmaceuticals (Licensee)
合成路线:In the first reaction step phenyl phosphate dichloride (I) and 2-chloroethylamine hydrochloride are reacted in dichloromethane with triethylamine as base to give phenyl N,N'-di-(2-chloroethyl)phosphoric acid diamide (II).Hydrogenation of compound (II) with platinic oxide/hydrogen in methanol yields N,N'-di-(2-chloroethyl)phosphoric acid diamide (III),which directly crystallizes in the methanolic solution.2,3,4,6-6-Tetra-O-benzyl-alpha-D-glucopyranose (IV) and trichloroacetonitrile react in ethyl acetate with sodium hydride as catalyst to yield O-(2,3,4,6-tetra-O-benzyl-alpha-D-glucopyranosyl) trichloroacetimidate (V).A mixture of the imidate (V) and compound (III) in ethyl acetate is warmed up to 60 C.After filtration and concentration,2,3,4,6-tetra-O-benzyl-beta-D-glucopyranosyl N,N'-di-(2-chloroethyl)phosphoric acid diamide (VI) crystallizes.Finally,compound (VI) is hydrogenated with palladium catalyst in acetone/water (80:20) to give beta-D-glucopyranosyl N,N'-di-(2-chloroethyl)phosphoric acid diamide.The solution is filtered and concentrated.The residual water is lyophilisated and the lyophilisate is crystallized in acetone/water.