文摘
A synthetic process for 2鈥?C-methylcytidine-5鈥?[2-[(3-hydroxy-2,2-dimethyl-1-oxopropyl)thio]ethyl-N-benzylphosphoramidate], a nucleotide prodrug inhibitor of hepatitis C virus NS5B polymerase, is described. The route developed was demonstrated on 100 g scale and featured the key application of phenylboronic acid as an effective transient means to protect the 2鈥?3鈥?hydroxyls of 2鈥?C-methylcytidine. This synthetic methodology resulted in a reduction in the number of isolations from five to two and an increase in the overall yield by 50% relative to the original unscalable discovery route. The synthesis and characterization of 2鈥?C-methylcytidine-2鈥?3鈥?O-phenylboronate is also provided.