Alternative Route for the Synthesis of New Derivatives of Benzimidazo[2′,1′:2,3] thiazolo[5,4-d]pyrimidine

Abstract

The benzimidazole core is classified by medicinal chemists as one of the privileged sub-structures for drug design, in the light of the affinity they display for a variety of enzymes and protein receptors. 1 Benzimidazoles are very important compounds due to their wide spectrum of biological activities such as antioxidant, 2 antimicrobial, 3 antihypertensive, 4 antiviral, 5 antifungal, 6 antitumour, 7 antihepatitis B virus, 8 anticancer, 9 anticonvulsant, 10 analgesic 11 and antiinflammatory 12 activities.Also, diverse biological properties have been associated with thiazolobenzimidazole derivatives, including antibacterial, 13,14 antifungal, 15 antiinflammatory, 16 antiulcer, 17 antiviral, 18 anthelmintic 19 and anticancer activity 20,21 . An in vitro parasitological study showed that the heterocyclic 2-substituted-[1,3] thiazolo[3,2-a]benzimidazole-3(2H)-ones exhibit higher activity than albendazole against Trichinella spiralis. 22 Moreover, benzimidazothiazolopyrimidines as potential biologically active heterocycles have been the subject of recent studies. 23,24 The synthetic routes to these compounds are limited and mainly involve cyclocondensation of 3-amino-2,3-dihydrobenzimidazo[2,1-b]thiazole-2-carbonitrile with electrophilic reagents such as formamide, acetic anhydride, and orthoesters in combination with amines. 25 Derivatives of these compounds have also been prepared through nucleophilic substitution reactions of the chlorine and alkylthio substituents with different nucleophiles such as hydrazine, thiourea and amines. 23 The above observations prompted us to report an alternative route for the synthesis of new derivatives of benzimidazothiazolopyrimidines through the reaction of the pyrimidine ring with 2-mercaptobenzimidazole. Results and discussionThe starting material 5-bromo-2,4-dichloro-6-methylpyrimidine 1 was prepared according to the published method. 26 Treatment