Klein’s Remdesivir-Nucleobase Synthesis Revisited: Chemoselective Cyanation of Pyrrol-2-carboxaldehyde

Abstract

4-Aminopyrrolo[2,1-f][1,2,4]triazine is a fundamental raw material in the synthesis of remdesivir, which demand has increased due to the tests and potential repositioning of this drug against Coronavirus disease 2019 (COVID-19). Here, three chemical steps route for the preparation of remdesivir’s nucleobase is described. Particularly, a highly chemoselective cyanation of Klein’s route and successful application of monochloramine prepared from commercial bleach as an N-amination reagent are presented.

Evolution of the Synthesis of Remdesivir. Classical Approaches and Most Recent Advances

“…Remdesivir sparked renewed interest in the synthesis of 12 . In an improved alternative (39% overall yield), the reaction of 8 and HOSA with NaHCO 3 afforded 11 (92% yield), and 10 was obtained in 71% yield by N -amination with NaH and ClNH 2 . However, the approach of Snead et al is the best one.…”