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

Sarabindu Roy (TCGLS Member), Ajay Yadaw (TCGLS Member), Subho Roy (TCGLS Member), Gopal Sirasani (TCG GC Member), Aravind Gangu (TCG GC Member), Jack D. Brown (TCG GC Member), Joseph D. Armstrong III (TCG GC Member), Rodger W. Stringham, B. Frank Gupton, Chris H. Senanayake* (TCG GC Member), and David R. Snead*Organic Process Research and Development (Published on 07th Jan 2022)

DOI: https://doi.org/10.1021/acs.oprd.1c00071

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.