Synthesis of new heterocyclic compounds containing hEGFR inhibitor candidate 3-aryl-5-alkyl-1h-1,2,4-triazole ring

In this study, which covers the synthesis part of the TÜBİTAK (1001) 118Z187 Project, amide hydrazone derivatives (131-133) were synthesized starting from iminoester hydrochlorides (130a, b). 3-Aryl-5-alkyl-1H-1,2,4-triazole derivatives (134-136) were obtained as a result of the ring closing reaction of these compounds (131-133) by heating them to dry conditions at approximately 180 °C a certain period of time. In the next step, 3-aryl-5-alkyl-1H-1,2,4-triazol-4-yl-acetate derivatives (137-139) were synthesized by the reaction of 1H-1,2,4-triazol with ethylbromoacetate in the presence of sodium ethoxide and these compounds were converted to acetohydrazide derivatives (140-142). In the next step, thiosemicarbazide derivatives (143-152) were obtained from the reaction of acetohydrazides (140-142) with appropriate isothiocyanates. In the last step of the study, 1,2,4-triazole-3-thion derivatives (153-162) containing 3-aryl-5-alkyl-1,2,4-triazole ring were synthesized by ring closing reaction of thiosemicarbazides (143-152) in the presence of NaOH (aq). The structures of the new compounds were elucidated by FT-IR, 1H NMR and 13C NMR spectroscopic methods.