An Efficient Synthesis of Exo-N-carbamoyl Nucleosides: Application to the Synthesis of Phosphoramidate Prodrugs

摘要

An efficient protection protocol for the 6-exo-amino group of purine nucleosides with various chloroformates was developed utilizing N-methyl imidazole (NMI). The reaction of an exo-N⁶-group of adenosine analog 1 with alkyl/ and aryl chloroformates under optimized conditions provided the N⁶-carbamoyl adenosines (2a-j) in good to excellent yields. The reaction of N⁶-Cbz-protected nucleosides (5a-c) with phenyl phosphoryl chloride (7) using t-BuMgCl followed by catalytic hydrogenation afforded the corresponding phosphoramidate pronucleotides (8a-c) in excellent yield.