Synthesis of ABBV-168, a 2'-Bromouridine for the Treatment of Hepatitis C.
Eric A VoightBrian S BrownStephen N GreszlerGeoff T HalvorsenGang ZhaoAlbert W KrugerJohn HartungKirill A LukinSteven R MartinezEric G MoschettaMichael T TudescoNathan D IdePublished in: The Journal of organic chemistry (2018)
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.