Synthesis of 2′-Methyl-6-methoxyguanosine from the Parent Ribonucleoside Guanosine

A short and efficient synthesis of the nucleoside fragment contained in the NS5B nucleoside inhibitor BMS-986094 was achieved in 23% overall yield on a gram scale. The synthesis uses the widely available starting material guanosine via a short sequence ending in a Mukaiyama hydration reaction to establish the key tertiary alcohol moiety and set the C-2′ methyl stereogenic center. This work resulted in a robust and scalable approach to this complex nucleoside.