Development of a Robust Manufacturing Route for Molnupiravir, an Antiviral for the Treatment of COVID-19.

Herein is described the development of a large-scale manufacturing process for molnupiravir, an orally dosed antiviral that was recently demonstrated to be efficacious for the treatment of patients with COVID-19. The yield, robustness, and efficiency of each of the five steps were improved, ultimately culminating in a 1.6-fold improvement in overall yield and a dramatic increase in the overall throughput compared to the baseline process.

Mild Synthesis of Substituted 1,2,5-Oxadiazoles Using 1,1'-Carbonyldiimidazole as a Dehydrating Agent.

1,1'-Carbonyldiimidazole was found to induce the formation of a variety of 3,4-disubstituted 1,2,5-oxadiazoles (furazans) from the corresponding bisoximes at ambient temperature. This method enables these inherently energetic compounds to be prepared at temperatures well below their decomposition points and with improved functional group compatibility relative to prior methods. Conditions were developed that allowed for the first high-yielding synthesis of chlorofurazans from their amino counterparts, enabling the mild synthetic manipulation of these heterocycles.