Enaminones as Building Blocks in Heterocyclic Preparations: Synthesis of Novel Pyrazoles, Pyrazolo[3,4-d]pyridazines, Pyrazolo[1,5-a]pyrimidines, Pyrido[2,3-d]pyrimidines Linked to Imidazo[2,1-b]thiazole System

Abstract

The unreported 2-[E-3-(N,N-dimethylamino)acryloyl]-3-methyl-5,6diphenylimidazo[2,1-b]thiazole 3 was prepared via the reaction of 2-acetyl-3methyl-5,6-diphenylimidazo[2,1-b]thiazole 2 with dimethylformamide dimethyl acetal (DMF-DMA). Enaminone 3 underwent regioselective 1,3-dipolar cycloaddition with nitrilimines 5a-f, to afford the corresponding pyrazoles 7a-f. The reaction of 7a,d,g with hydrazine hydrate, afforded the pyrazolo[3,4d]pyridazines 8a-c, respectively. Enaminone 3 also reacted with a hydrazines, hydroxylamine hydrochloride, 5-aminopyrazole 11, 6-aminothiouracil 15 and hippuric acid 22. The structures of the newly synthesized compounds were confirmed by spectral data and elemental analyses. Enaminones are poly-dentate reagents that have been utilized extensively in this decade as building blocks in organic synthesis. Furthermore, many enaminones were found to exhibit several biological activities as antitumor, antibacterial and anticonvulsant agents. On the other hand, imidazoles possess important biological, pharmacological and therapeutic activities, where midazoles are present in compounds that have antiasthmatic, anti-inflammatory, antiulcerative, antithrombotic, fungicidal and herbicidal activities. Furthermore, some imidazo[2,1b]thiazoles were active against various cancer cell lines. Much interest has also been focused on the chemistry and anticonvulsant, analgesic, antibacterial and antisecretory activities displayed by HETEROCYCLES, Vol. 85, No. 9, 2012 2291