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

摘要

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 3-6 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.