Article

Strategy for the Synthesis of Pyridazine Heterocycles and Their Derivatives

Rega Institute for Medical Research, Laboratory of Medicinal Chemistry, Katholieke Universiteit Leuven, Minderbroedersstraat 10, B-3000 Leuven, Belgium
Galapagos, Laboratory of Medicinal Chemistry, Generaal De Wittelaan L11 A3, B-2800 Mechelen, Belgium
J. Org. Chem., 2013, 78 (16), pp 7845–7858
DOI: 10.1021/jo400989q
Publication Date (Web): July 31, 2013
Copyright © 2013 American Chemical Society
*E-mail: piet.herdewijn@rega.kuleuven.be. Tel: +32 (0)16/33.73.87. Fax: +32 (0)16/33.73.40.

Abstract

Abstract Image

The first synthesis of novel fused pyridazines has been realized starting from 1,3-diketones involving a Diaza–Wittig reaction as a key step. A convenient strategy was elaborated to access versatile pyridazine derivatives allowing the variation of substituents at position 6 of the heterocyclic ring. In a first part, pyridazines bearing an ester group were synthesized as a model to evaluate the methodology. In a second part, an improved procedure has been used for the synthesis of pyridazines bearing a ketone group and different methods of cyclization were carried out, leading to several hitherto unknown biheterocyclic compounds. This reaction scheme represents an attractive methodology for the synthesis of novel fused pyridazine derivatives.

Supporting Information


1H NMR and 13C NMR spectra of compounds 10, 15, 16, 18, 19, 21, and 2228, as well as LC/MS analysis of compounds 24bj, 25af, 26ad, 27ah, and 28a,b. This material is available free of charge via the Internet at http://pubs.acs.org.

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Received 6 May 2013
Published online 31 July 2013
Published in print 16 August 2013
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