Pergamon Tetrahedron Letters 41 (2000) 1027–1030 TETRAHEDRON LETTERS Multistep synthesis of thiazoloquinazolines under microwave irradiation in solution Thierry Besson, a,* Jérôme Guillard a and Charles W. Rees b a Laboratoire de Génie Protéique et Cellulaire, UPRES 2001,Groupe de Chimie Organique, Pôle Sciences et Technologie, Université de La Rochelle, Avenue Marillac, F-17042 La Rochelle cedex 1, France b Department of Chemistry, Imperial College of Science, Technology and Medicine, London SW7 2AY, UK Received 28 October 1999; accepted 26 November 1999 Abstract Thiazolo[5,4-f]quinazolines are synthesised in six or seven steps from 2-amino-5-nitrobenzonitrile. Both he- terocyclic rings are fused onto the central benzene ring via imino-1,2,3-dithiazoles which are readily obtained from primary aromatic amines and 4,5-dichloro-1,2,3-dithiazolium chloride (Appel salt). Four of the steps were improved in yield or reaction time or both, compared to conventional heating, by microwave irradiation of solutions of the reactants in a focused open microwave oven. © 2000 Elsevier Science Ltd. All rights reserved. Keywords: medium ring heterocycles; microwave heating; thiazoles; quinazolines. N-Arylimino-1,2,3-dithiazoles 2 are readily prepared in high yield from anilines and 4,5-dichloro- 1,2,3-dithiazole chloride 1. 1,2 These imines are highly versatile intermediates in heterocyclic synthesis, undergoing a variety of reactions initiated by nucleophilic attack at different sites on the dithiazole ring. For example, they can be converted into 2-cyano derivatives of benzothiazoles 3 or 4-alkoxyquinazolines 4 (Scheme 1). 2,3 In a search for new polyheterocyclic systems of potential pharmacological value, we have now combined these two processes in the synthesis of the rare thiazolo[5,4-f]quinazolines, by starting from a benzene derivative and fusing on both heterocyclic rings via iminodithiazoles. As part of our work on the application of microwave irradiation of reaction solutions, 4 we have transposed several of the present reactions to a focused microwave oven (open oven, monomode system) especially designed for organic synthesis, and have achieved striking reductions in reaction times, better yields and cleaner reactions than for the purely thermal processes. Conventional heating and microwave irradiation of the reactions are compared. Synthesis of the rare thiazolo[5,4-f]quinazoline ring was performed in six steps from commercially available 2-amino-5-nitrobenzonitrile (Scheme 2); preliminary studies showed that it is better to create the quinazoline ring before the thiazole ring. * Corresponding author. Fax: (33) (0)5 46 45 82 47; e-mail: tbesson@bio.univ-lr.fr (T. Besson) 0040-4039/00/$ - see front matter © 2000 Elsevier Science Ltd. All rights reserved. PII: S0040-4039(99)02221-2 tetl 16149