Phenylacetone as Building Blocks in Heterocyclic Synthesis: Synthesis of Polyfunctionally-Substituted Pyridines, and fused Pyridines

Abstract

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 α -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-dimethylacetal 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 .

Keywords:

• Pyrazolopyridines
• pyridines
• thienopyridines
• Tria(Tetra)azafluorine