Direct Synthesis of Multi-functional Pyrimidine, Pyrazine, and Pyridine Scaffolds via Inter- and Intramolecular Annulations of 3-Amino-thieno[2,3-b]pyridine-2-carboxylate

摘要

The synthesis of a new series of annulated thieno[2,3-b]pyridines was performed. Ester compound 1 underwent heterocyclization upon reaction with phenylisothiocyanate and formamide to afford pyrimidines 2 and 3, respectively. Thienopyrimidine 5 was resulted via reaction of amino derivative 1 with triethyl orthoformate to afford the non-isolable intermediate 4, which allowed hydrazinolysis with hydrazine hydrate to afford the target compound. Pyrimidine type 5 was condensed with p-nitrobenzaldehyde to afford Schiff base 6. Refluxing of ester 1 with ethyl cyanoacetate and diethyl malonate followed by base-mediated heterocyclization afforded condensed pyridines 8 and 9, respectively. The tetracyclic pyrazine derivative 14 was obtained from the reaction of amino compound 1 with 2,5-dimethoxytetrahydrofuran followed by hydrazinolysis to give carbohydrazide 11, which undergo diazotization followed by Curtius rearrangement. The antibacterial results illustrated no significant results for the investigated compounds except compound 5, which has moderate activity against Gram-positive bacteria.