ABSTRACT

A synthesis of two series of 3-substituted quinazolinones was performed utilizing a green chemistry approach, deep eutectic solvents and microwaves, namely. 2-Methyl-3-substituted-quinazolin-4(3H)-one derivatives were synthesized in a two-step reaction, using choline chloride:urea deep eutectic solvent (DES). 3-Substituted-quinazolin-4(3H)-ones were synthesized in one-pot one-step reaction of anthranilic acid, amines and orthoester in a microwave reactor. For the synthesis of 2-methyl-3-substituted-quinazolin-4(3H)-ones, first conventional synthesis of benzoxazinone, as an intermediate, was performed. Further, benzoxazinone in reaction with corresponding amines, in choline choline:urea deep eutectic solvent, furnished desired compounds. These procedures are based on green principles with the aim of developing synthetic routes for the potential antitumor agents. All compounds were characterized by LC/MS, ¹H NMR and ¹³C NMR spectral techniques. Compound 1 bearing trifluoromethoxyphenyl group showed promising activity against HuT-78 cell line with IC₅₀ of 51.4 ± 5.1 µM.

摘要

利用绿色化学方法，即深共熔溶剂和微波，进行了两个系列的3-取代的喹唑啉酮的合成。使用氯化胆碱：脲深共熔溶剂（DES）在两步反应中合成了2-甲基-3-取代-喹唑啉-4（3 H）-一衍生物。在微波反应器中，邻氨基苯甲酸，胺和原酸酯的一锅一步反应合成了3-取代的喹唑啉-4（3 H）-一。用于合成2-甲基-3-取代的喹唑啉-4（3 H）-，首先进行苯并恶嗪酮作为中间体的第一常规合成。此外，在胆碱胆碱：脲深的低共熔溶剂中，苯并恶嗪酮与相应的胺反应提供了所需的化合物。这些程序基于绿色原理，目的是为潜在的抗肿瘤药开发合成途径。所有化合物均通过LC / MS，¹ H NMR和¹³ C NMR光谱技术进行了表征。带有三氟甲氧基苯基的化合物1对HuT-78细胞系表现出良好的活性，IC ₅₀为51.4±5.1 µM。