Facile and Scalable Methodology for the Pyrrolo[2,1-f][1,2,4]triazine of Remdesivir

Pyrrolo[2,1-f][1,2,4]triazine (1) is an important regulatory starting material in the production of the antiviral drug remdesivir. Compound 1 was produced through a newly developed synthetic methodology utilizing simple building blocks such as pyrrole, chloramine, and formamidine acetate by examining the mechanistic pathway for the process optimization exercise. Triazine 1 was obtained in 55% overall yield in a two-vessel-operated process. This work describes the safety of the process, impurity profiles and control, and efforts toward the scale-up of triazine for the preparation of kilogram quantity.

Automated summary

This study presents a newly developed synthetic methodology for the production of Pyrrolo[2,1-f][1,2,4]triazine, an important starting material for the antiviral drug remdesivir. Through examining the mechanistic pathway, simple building blocks such as pyrrole, chloramine, and formamidine acetate were successfully utilized to obtain triazine 1 with an overall yield of 55% in a two-vessel-operated process. The research also focuses on the safety of the process, impurity profiles and control, and efforts towards scale-up for large-scale production.