ARYL H-PHOSPHONATES .6. SYNTHETIC STUDIES ON THE PREPARATION OF NUCLEOSIDE N-ALKYL-H-PHOSPHONAMIDATES

Various approaches to the synthesis of nucleoside H-phosphonamidates h ave been investigated. Direct couplings of nucleoside H-phosphonates w ith amines have been hampered by extensive reactions of the condensing agents with amines. Preactivation of nucleoside H-phosphonates with p ivaloyl chloride or chlorophosphates, followed by the addition of amin es, notably diminished these side reactions. The most efficient and ve rsatile route to nucleoside N-alkyl H-phosphonates was found to be ami nolysis of the in situ-produced aryl nucleoside H-phosphonates with ap propriate amines.