Synthesis of ABBV-168, a 2′-Bromouridine for the Treatment of Hepatitis C

ABBV-168 is a dihalogenated nucleotide
under investigation for
the treatment of hepatitis C virus. Three synthetic routes aimed at
achieving the stereoselective installation of the C2′ gem-Br,F substitution and subsequent Vorbruggen glycosylation
were explored to prepare the penultimate nucleoside intermediate.
Development culminated in a route to ABBV-168 featuring a de novo
chromatography-free furanose synthesis, protecting group-directed
Vorbruggen glycosylation, and highly selective phosphoramidation to
furnish the API.