摘要
(R)-1,3-二甲基哌嗪-2-酮是AZD5153的重要分子砌块。本文设计并优化了该化合物的合成工艺,以2-(甲氨基)乙醇和碳酸二叔丁酯为起始原料,经酰胺化、氧化、亲核加成、氢化还原和分子内酰胺化等步骤得到目标化合物。所得化合物的结构经^(1)H NMR、^(13)C NMR和HRMS确证。反应总收率为75.4%。优化后的工艺条件温和、操作简单、环境污染小,更加适合工业化生产。
(R)-1,3-Dimethylpiperazin-2-one is an important molecular building block of AZD5153.In this study,the synthesis process of this compound was designed and optimized using 2-(methylamino)ethanol and di-tert-butyl dicarbonate as starting materials.The target compound was obtained through a series of steps including amidation,oxidation,nucleophilic addition,hydrogenation reduction,and intramolecular amidation.The structure of the obtained compound was confirmed by ^(1)H NMR,^(13)C NMR,and HRMS.The overall reaction yield was 75.4%.The optimized process conditions were mild,simple to operate,environmentally friendly,and more suitable for industrial production.
作者
汤世鑫
王泓印
任永远
蔡东
TANG Shi-xin;WANG Hong-yin;REN Yong-yuan;CAI Dong(College of Pharmacy,Jinzhou Medical University,Jinzhou 120001,China;Shanghai Changfeng Biomedical Technology Co.,Ltd,Shanghai 201401,China)
出处
《化学研究与应用》
北大核心
2025年第9期2810-2816,共7页
Chemical Research and Application
作者简介
通讯作者:蔡东(1978-),男,教授,主要从事药物小分子设计、合成及活性筛选。E-mail:Caid@jzmu.edu.cn。
