Cyanoacetamide in heterocyclic chemistry: Synthesis, antitumor and antioxidant activities of some new benzothiophenes

Cyanoacylation of 2‐amino‐tetrahydrobenzothiophene‐3‐carboxylate ethyl ester with 3‐(3,5‐dimethyl‐1H‐pyrazol‐1‐yl)‐3‐oxopropanenitrile afforded cyanoacetamide 2. The later was utilized as key intermediate for the synthesis of 3‐substituted 2‐iminocoumarins 3, 4, 5, 6 and acrylamides 7a, b via Knoevenagel condensation with 2‐hydroxy‐1‐naphthaldehyde; 2‐hydroxybenzaldehyde; 1‐nitrosonaphthalen‐2‐ol; 7‐hydroxy‐5‐methoxy‐2‐methyl‐4‐oxo‐4H‐chromene‐6‐carbaldehyde; 4‐dimethylamino‐benzaldehyde; and 4‐piperidin‐1‐yl‐benzaldehyde in EtOH/piperidine. The derivatives 7a, b did not afford the pyrazoles 8a, b upon treating with phenyl hydrazine. Furthermore, coupling of 2 with 4‐amino‐1,5‐dimethyl‐2‐phenyl‐1H‐pyrazol‐3(2H)‐one and 4,6‐dimethyl‐1H‐pyrrolo[2,3‐b]pyridin‐3‐amine afforded the hydrazone derivatives 9 and 10, respectively. The later derivative 10 was cyclized in acetic acid to afford the pyridopyrazolotriazine 11. Finally, 2 was treated with dimethylformamide‐dimethylacetal (DMF‐DMA) to afford the dimethylaminoacrylamide 12 which underwent transamination with 4,6‐dimethyl‐1H‐pyrrolo[2,3‐b]pyridin‐3‐amine to afford the pyrazole 13. Cyclization of compound 13 in acetic acid or pyridine was unsuccessful. The antitumor and antioxidant activities of the synthesized products were evaluated; several were found to exhibit promising antioxidant activities. J. Heterocyclic Chem., (2011).