F. Piscitelli, G. L. Regina, R. Silvestri
Apr 1, 2008
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Influential Citations
4
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Journal
Organic Preparations and Procedures International
Abstract
Indolyl arylsulfones (IASs) are potent non-nucleoside inhibitors of HIV1 reverse transcriptase (RT).' Compound 1 bearing the 5-chloro-4-fluoro substitution pattern at the indole ring, was exceptionally potent against RT WT and RTs carrying drug-resistant mutations. We selected 1 as a lead compound for the development of new second-generation analogues (Fig l)? In 2002, we described a procedure for the synthesis of ethyl 5-chloro-4-fluoro-1Hindole-2-carboxylate (2) and ethyl 5-chloro-6-fluoro1 H-indole-2-carboxylate (3)3 through compound 5 obtained by N-chlorosuccinimide chlorination of the ethyl pyruvate 3-fluorophenylhydrazone (4) prepared from 3-fluoroaniline via the Japp-Klingemann4 procedure. Fischefl cyclization of 5 in the presence of polyphosphoric acid (PPA) as a catalyst, gave the indole esters 2 and 3 which could be separated by repeated chromatography columns (Scheme 1) . However, since compound 2 was obtained as minor isomer by this procedure? we investigated a more convenient synthesis. We could not find literature describing the synthesis of 4,5-dihalodisubstituted indole-2-carboxylate as the sole