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A Protocol for Analyzing Hepatitis C Virus Replication
Published on: June 26, 2014
Synthesis of ABBV-168, a 2'-Bromouridine for the Treatment of Hepatitis C
Eric A Voight1, Brian S Brown1, Stephen N Greszler1
1Discovery Chemistry and Technology , AbbVie, Inc. , 1 North Waukegan Road , North Chicago , Illinois 60064-1802 , United States.
Abstract:
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.
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