Efficient Synthesis of Gemcitabine 5 '-O-Triphosphate Using Gemcitabine 5 '-O-Phosphoramidate as an Intermediate

A new efficient approach for the synthesis of gemcitabine triphosphate has been developed. The method is based on the ring-opening reaction of 2-cyanoethoxy-2-oxo-1,3,2-oxathiaphospholane with protected gemcitabine in the presence of DBU. Subsequent treatment of gemcitabine monophosphate with DCC in the presence of ammonia provides gemcitabine 5'-O-phosphoramidate. Finally, this compound, on reaction with pyrophosphate, furnishes gemcitabine 5'-triphosphate in 50% yield.