合成路线1

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.