Triazine

Intermediate

Summary

This publication is to provide technical information on M4ALL’s two-pot protocol for the preparation of pyrrolotriazine, toward a supply centered synthesis of remdesivir. This route features atom economy and reduced derivatization of starting materials, by making use of highly abundant, commoditized raw material inputs. The yield of triazine was doubled from 33% to 59%, and the synthetic step count was reduced from 4 to 2. A one-pot cascade sequence was developed for direct cyanation of pyrrole, and the problematic nature of typically dilute electrophilic aminations was solved with semi-continuous processing. Moreover, development of a continuous platform afforded access to the ideal yet non-commercial aminating reagent, monochloramine. Unit operations are minimized by telescoping reactions. These efforts help to secure the Remdesivir supply chain.

Triazine

Triazine