Phenylacetone as building blocks in heterocyclic synthesis: Synthesis of polyfunctionally-substituted pyridines, and fused pyridines

Many pyridinethiones are biologically active. In view of our interest in developing efficient syntheses of polyfunctionally substituted heteroaromatics utilizing the readily obtainable enaminone 3 as starting materials. So, treatment of enaminone 3 with cyanothioacetamide or cyanoacetamide afforded the pyridinethione 5a and pyridone 5b. compound 5a reacted with alpha-halo- ketones in refluxing sodium ethoxide to give the thienopyridine derivatives 9a-e. Compound 5a reacted with methyl iodide to give 2-methylthiopyridine 10. Condensation of pyridinethione 5a with dimethylformamide-dimethylacetaI gave the adduct 11 and with hydrazine hydrate afforded 12. Compound 5a reacted with arylidenemalonitrile to give styryl derivatives 14a-d. Compound 14a-d also prepared from the condensation of 5a with the aromatic aldehydes under the same condition. Reflux of thienopyridine derivatives 9a-d with triethylorthoformat, acetic anhydride, carbon disulfide and sodium nitrite to give compounds 19-23, respectively. The aminopyrazole 12 reacted with dimethylaminopropiophenone hydrochloride 24 or enaminone 30 in refluxing DMF to yield compound 26a-d. Treatment of 12 with 32 afforded 34. Compound 34 can be also prepared from the reaction of 37 with aroylacetonitrile 31. Compound 12 reacted with DMF-DMA to give 37, which reacted with compound 1 to give 38 prepared directly from reaction of 12 with enaminone 2. Diazotization of 12 with nitrous acid followed by coupling with different active methylene reagents afforded the pyridothienotriazines 42a,b. Reaction of benzylideneacetophenone with 12 yielded the pyridopyrazolopyrimidine 44. Also, compound 12 reacted directly with active methylene to give the pyridopyrazolopyrimidine derivatives 46a,b.