合成路线1

The silylated ethyl glycolate (I) is transformed into the cyclopropyl alcohol (II) by using the Kulinkovich reaction in the presence of ethylmagnesium bromide and titanium isopropoxide. Alcohol (II) is then condensed with diisopropyl (bromomethyl)phosphonate (III) to produce the alkoxymethyl phosphonate (IV). After desilylation of (IV) with ammonium fluoride, the free alcohol (V) is treated with methanesulfonyl chloride and triethylamine to provide mesylate (VI). Condensation of (VI) with 2-amino-6-chloropurine (VII) leads to the 9-substituted purine (VIII) as the major reaction product. Removal of the 6-chloro group of (VIII) by catalytic hydrogenolysis furnishes purine (IX). The phosphonate ester of (IX) is hydrolyzed to phosphonic acid (X) employing bromotrimethylsilane. Finally, condensation of (X) with chloromethyl pivalate (XI) in the presence of either N,N'-dicyclohexyl-4-morpholine-carboxamidine (DCMC) or triethylamine gives rise to the title compound