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Synthesis 2001(12): 1806-1811
DOI: 10.1055/s-2001-17526
PAPER
© Georg Thieme Verlag Stuttgart · New York

Syntheses of 4-Benzylpyridones via Nucleophilic Aromatic Substitutions

Yves L. Janin*a, Christiane Huelb, Michel Legraverendb, Anne-Marie Aubertinc, Emile Bisagnib
a UMR 176 CNRS-Institut Curie, 26 rue d"Ulm, 75248 Cedex 05, Paris, France
Fax: +33(1)42346631; e-Mail: Yves.Janin@curie.u-psud.fr;
b UMR 176 CNRS-Institut Curie and (c) U 350 INSERM-Institut Curie, Bat. 110 Campus Universitaire, F-91405 Orsay, France
c INSERM U74 Institut de Virologie, 3 rue Koeberlé, F-67000 Strasbourg, France
Further Information

Publication History

Received 7 June 2001
Publication Date:
11 August 2004 (online)

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Abstract

Different strategies were studied for the preparation of analogues of potent biarylmethanes non-nucleoside reverse transcriptase inhibitors. We undertook the study of the possible routes for the preparation of 3-cyano-4-(3,5-dimethylbenzyl)-5-ethyl-6-hydroxypyridin-2(1H)-one and its cyclic analogue 4-(3,5-dimethylbenzyl)- 6-oxo- 2,3,6,7 - tetrahydrofuro [2,3 - b] pyridine-5 - carboni-trile. Preparation of the former was achieved from the anion of 4-methyl-5-ethyl-2,6-dimethoxynicotinonitrile either by a nucleophilic aromatic substitution reaction on 3,5-dimethyl iodobenzene or starting with a nucleophilic addition reaction on 3,5-dimethylcyclohexanone. Cyclic analogues were prepared by an unprecedented nucleophilic aromatic substitution of, for example, 3,5-dimethyliodobenzene with the dianion of 4-methyl-6-oxo-2,3,6,7-tetrahydrofuro[2,3-b]pyridine-5-carbonitrile. None of the herein described new compounds showed anti HIV-1 activity or cytotoxicity on cellular assays (CEM-SS and MT4).

Key words

HIV-1 - pyridines - arylation - nucleophilic aromatic substitution - SRN1

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