Improvement of the C-glycosylation Step for the Synthesis of Remdesivir

Abstract

The bulk supply of the antiviral C-nucleoside analogue remdesivir is largely hampered by a low-yielding C-glycosylation step in which the base is coupled to the pentose unit. Here, we disclose a significantly improved methodology for this critical transformation. By utilizing diisopropylamine as a cost-effective additive, the addition reaction furnishes an optimal yield of 75% of the desired ribofuranoside adduct, representing the highest yield obtained thus far for this key step. The method proved suitable for hectogram scale synthesis without column chromatographic operations.