Facile and Scalable Methodology for the Pyrrolo[2,1- <i>f</i> ][1,2,4]triazine of Remdesivir
Sarabindu Roy, Ajay Yadaw, Subho Roy, Gopal Sirasani, Aravind S. Gangu, Jack D. Brown, Joseph D. Armstrong, Rodger W. Stringham, B. Frank Gupton, Chris H. Senanayake, David R. Snead
Abstract
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.