Division of Chemistry, Department of Science and Humanities, Vignan`s Foundation for Science, Technology and Research -VFSTR (Deemed to be University), Vadlamudi, Guntur, 522 213, Andhra Pradesh, India.
CoExAMMPC, Vignan`s Foundation for Science, Technology and Research -VFSTR (Deemed to be University).
Curr Org Synth. 2022 Aug 6;19(5):578-582. doi: 10.2174/1570179419666211230094334.
1,2,4-triazoles scaffolds display significant biological activities due to hydrogen bonding, solubility, dipole character, and rigidity.
The core motif of 1,2,4-triazoles plays a vital role in clinical drugs such as Rizatriptan (antimigraine), Ribavirin (antiviral), anastrozole (anticancer), etizolam (anxiolytic), estazolam (anticonvulsant), alprazolam (anti-hypnotic), letrozole (aromatase inhibitor), loreclezole (anticonvulsant), trazadone (antidepressant) etc. Methods: Epoxide ring opening of tert-butyl 6-oxa-3-azabicyclo [3.1.0] hexane-3-carboxylate followed by methylation under basic conditions and de-protection gave the corresponding trans 1-(4- methoxypyrrolidin-3-yl)-1H-1,2,4-triazole hydrochloride salt as the precursor. This precursor on reaction with substituted benzoyl chlorides and benzyl bromides gave the desired amide and amine products.
A library of 14 N-substituted pyrrolidine derivatives i.e. trans3-methoxy-4-(1H-1,2,4-triazol- 1-yl) pyrrolidin-1-yl) (phenyl)methanone and trans 1-benzyl-4-methoxypyrrolidin-3-yl)-1H-1,2,4- triazole were prepared.
Eight novel amides (6a-h) and six amines (8a-f) derivatives were synthesized using 1-(4- methoxypyrrolidin-3-yl)-1H-1,2,4-triazole 4 salt with substituted benzoyl chlorides and benzyl bromides.
1,2,4-三唑骨架由于氢键、溶解度、偶极性质和刚性，显示出显著的生物活性。
1,2,4-三唑的核心结构在利扎曲坦（抗偏头痛）、利巴韦林（抗病毒）、阿那曲唑（抗癌）、依替唑仑（抗焦虑）、依唑仑（抗惊厥）、阿普唑仑（抗催眠）、来曲唑（芳香酶抑制剂）、洛尔唑仑（抗惊厥）、曲唑酮（抗抑郁）等临床药物中发挥着重要作用。
叔丁基 6-氧代-3-氮杂双环[3.1.0]己烷-3-羧酸酯开环后在碱性条件下进行甲基化和脱保护，得到相应的反式 1-(4-甲氧基吡咯烷-3-基)-1H-1,2,4-三唑盐酸盐作为前体。该前体与取代的苯甲酰氯和溴化苄反应得到所需的酰胺和胺产物。
合成了 14 个 N-取代的吡咯烷衍生物，即反式 3-甲氧基-4-(1H-1,2,4-三唑-1-基)吡咯烷-1-基)（苯基）甲酮和反式 1-苄基-4-甲氧基吡咯烷-3-基)-1H-1,2,4-三唑。
用 1-(4-甲氧基吡咯烷-3-基)-1H-1,2,4-三唑 4 盐与取代的苯甲酰氯和溴化苄反应合成了 8 个新酰胺（6a-h）和 6 个胺（8a-f）衍生物。
