Synthesis of Substituted Imidazo[1,5-a]pyridines Starting from N-2-Pyridylmethylamides Using Lawesson’s Reagent and Mercury(II) Acetate

Aline Moulin; Sandra Garcia; Jean Martinez; Jean-Alain Fehrentz

doi:10.1055/s-2007-983852

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Synthesis of Substituted Imidazo[1,5-a]pyridines Starting from N-2-Pyridylmethylamides Using Lawesson’s Reagent and Mercury(II) Acetate

Aline Moulin, Sandra Garcia, Jean Martinez, Jean-Alain Fehrentz*
Institut des Biomolécules Max Mousseron, UMR 5247 Faculté de Pharmacie, CNRS - Universités Montpellier I et II, 15 avenue Charles Flahault, BP 1441, 34093 Montpellier Cedex 5, France
Fax: +33(4)67548654; e-Mail: jean-alain.fehrentz@univ-montp1.fr;

Abstract

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Abstract

A new method for the synthesis of substituted imidazo[1,5-a]pyridines (2-azaindolizines) starting from carboxylic acid and 2-methylaminopyridine is described. The reaction of the obtained N-2-pyridylmethylamides with Lawesson’s reagent generated the target imidazopyridines, along with the corresponding thioamide intermediates. After a simple filtration on alumina, addition of mercury(II) acetate allowed for total conversion of the thioamides into the imidazopyridines. The reaction conditions, as well as the influence of the substituent in position 3 of the imidazopyridine ring were explored. We also demonstrated that this heterocyclization was racemization free in the presence of a chiral carbon in position α to the heterocycle.

Key words

heterocycles - imidazo[1,5-a]pyridines - 2-azaindolizines - Lawesson’s reagent - mercury(II) acetate

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