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

Pyrrolo[2,1-][1,2,4]triazine () is an important regulatory starting material in the production of the antiviral drug remdesivir. Compound 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 was obtained in 55% overall yield in a two-vessel-operated process.

Development of a Scalable, Chromatography-Free Synthesis of t-Bu-SMS-Phos and Application to the Synthesis of an Important Chiral CF-Alcohol Derivative with High Enantioselectivity Using Rh-Catalyzed Asymmetric Hydrogenation.

A chromatography-free, asymmetric synthesis of the C2-symmetric P-chiral diphosphine t-Bu-SMS-Phos was developed using a chiral auxiliary-based approach in five steps from the chiral auxiliary in 36% overall yield. Separtion and recovery of the auxiliary were achieved with good yield (97%) to enable recycling of the chiral auxiliary. An air-stable crystalline form of the final ligand was identified to enable isolation of the final ligand by crystallization to avoid chromatography.