Aryl <i>H</i>-Phosphonates. 6. Synthetic Studies on the Preparation of Nucleoside <i>N</i>-Alkyl-<i>H</i>-phosphonamidates

Abstract

Various approaches to the synthesis of nucleoside H -phosphonamidates have been investigated. Direct couplings of nucleoside H -phosphonates with amines have been hampered by extensive reactions of the condensing agents with amines. Preactivation of nucleoside H -phosphonates with pivaloyl chloride or chlorophosphates, followed by the addition of amines, notably diminished these side reactions. The most efficient and versatile route to nucleoside N -alkyl H -phosphonates was found to be aminolysis of the in situ -produced aryl nucleoside H -phosphonates with appropriate amines.