Cyclization of the hydroxy phosphonic acid (I) (Cidofovir) with DCC in the presence of N,N-dicyclohexyl-4-morpholine carboxamidine (DCMC) (II) led to the cyclic phosphonate DCMC salt (III). Subsequent alkylation of (III) with 1-bromo-3-hexadecyloxypropane (IV) provided the corresponding phosphate ester (V). Finally, ring opening of the cyclic phosphonate was accomplished by treatment with aqueous NaOH.
Cidofovir (I) is converted to the cyclic phosphonate derivative (II) upon treatment with dicyclohexylcarbodiimide (DCC) in the presence of N,N-dicyclohexyl-4-morpholinecarboxyamidine (DCMC). Reaction of (II) with 1-bromo-2-(octadecyloxy)ethane (III) provides the corresponding phosphonate ester (IV). Finally, opening of the cyclic phosphonate to furnish the title compound is accomplished by treatment with 0,5 M NaOH