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Synthesis of Remdesivir by Direct Lithiation of Pyrrolo[2,1‐f][1,2,4]triazine Derivatives Enabled C‐Glycosylation

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A direct and regioselective lithiation was realized on N-Boc-pyrrolo[2,1-f][1,2,4]triazine, simply utilizing the distinct sigma-acidity on C-9. Starting from this enabling discovery, C-glycoside formation, cyanation, and global deprotection steps constitute one of the most efficient syntheses of GS-441524. Furthermore, transient protection was applied on GS-441524 with phenyl boronic acid, which facilitated a powerful one-pot synthesis of remdesivir.


Abstract

A direct and regioselective lithiation was realized on N-Boc-pyrrolo[2,1-f][1,2,4]triazine, simply utilizing the distinct sigma-acidity on C-9. Starting from this enabling discovery, C-glycoside formation, cyanation, and global deprotection steps constitute one of the most efficient syntheses of GS-441524. Furthermore, transient protection was applied on GS-441524 with phenyl boronic acid, which facilitated a powerful one-pot synthesis of remdesivir.

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