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.

A general method for the synthesis of unsymmetrically substituted ureas via palladium-catalyzed amidation.

A general and practical method for the preparation of unsymmetrically substituted ureas has been developed utilizing palladium-catalyzed amidation. Both aryl bromides and chlorides, as well as heteroaryl chlorides, have been coupled to aryl, benzyl, and aliphatic ureas by using a novel nonproprietary bipyrazole ligand (bippyphos).

Direct Metalation of 1,3,5,7-Tetranitrocubane with Amides of Tin and Lead. Preparation and Chemistry of o-Nitrostannanes and o-Nitroplumbanes in the Cubyl Series(1).

Trialkyltin and trialkyllead amides react directly and remarkably easily with 1,3,5,7-tetranitrocubane to form mono- to tetrakis(trialkyltin)- and -(trialkyllead) tetranitrocubanes. These are all stable compounds. The X-ray crystallographic properties of some are given. The (trialkylstannyl)cubanes react with electrophiles such as bromine with unexpected cleavage of alkyltin bonds rather than cubyl-tin bonds. On the other hand, the (trialkylplumbyl)cubanes do ultimately undergo cubyl-lead bond cleavage. This provides a useful way to achieve substitution on the cubane nucleus and provides access to compounds such as 1,3,5,7-tetrabromo-2,4,6,8-tetranitrocubane. The lead derivatives of tetranitrocubane are also useful for making 1,2,3,5,7-pentanitrocubane and 1,2,3,4,5,7-hexanitrocubane.