The synthesis of 3,5-diaryl-1,2,4-triazol substituted 1,2,4-triazol-3-thion derivatives with hEGFR inhibition potential

In this study, the synthesis of new 1,2,4-triazole-3-thion derivatives containing 3,5-diaryl-1,2,4-triazole ring with hEGFR inhibitory potential and was aimed. For this purpose; In the first part of the study, hydrazone compounds (144, 145) as a result of the reactions of ethyl imidobenzoate hydrochloride (143) with appropriate hydrazides; 4-amino-4H-1,2,4-triazole (146, 147) derivatives from the reaction of hydrazone compounds (144, 145) with hydrazine hydrate in the presence of 1-propanol; By treating them (146, 147) with sodium nitrite in hypophosphorous acidic medium, 1H-1,2,4-triazole derivatives (148, 149) were synthesized according to the methods registered in the literature. Then, 1H-1,2,4-triazole derivatives (148, 149) were converted to 1H-1,2,4-triazol-4-yl acetate compounds (150, 151) by reaction with ethyl bromoacetate in sodium ethoxide medium. In another step of the study, acetohydrazide compounds (152, 153) containing 1,2,4-triazole ring were obtained by treating ethylacetate derivatives (150, 151) with hydrazine hydrate in 1-butanol medium. In the next step, the corresponding thiosemicarbazide derivatives (154-163) were obtained from the reaction of acetohydrazide derivatives (152-153) with appropriate isothiocyanates, and these compounds were converted to 1,2,4-triazole-3-thione (164-173) derivatives by ring closure in the presence of NaOH (aq). The structures of all the newly synthesized compounds were elucidated by IR, 1H NMR and 13C NMR spectroscopic methods.