| 樊玲玲,罗忠福,罗碧兰,汤磊,李永.化学通报,2019,82(9):837-841. |
| CRBN调节剂Avadomide的合成工艺优化 |
| Optimization of Synthetic Process for The CRBN Regulator Avadomide |
| 投稿时间：2019-06-26 修订日期：2019-07-14 |
| DOI： |
| 中文关键词: CRBN调节剂， Avadomide，工艺优化 |
| 英文关键词:CRBN regulator, Avadomide, Process optimization |
| 基金项目:贵州省化学合成药物研发利用工程技术研究中心项目（黔科合［2016］平台人才5402）；贵州省普通高等学校药物化学工程研究中心项目（黔教合KY字［2014］219号）；贵州省卫生计生委科学技术基金项目（gzwjkj2016-1-050）；贵州省科技支撑计划项目（黔科合支撑[2017]2835，黔科合[2016]支撑2848）；贵州省科技计划项目（黔科合基础[2019]1269号）；贵州省研究生教育教学改革重点课题（黔教合YJSCXJH[2018]019）资助 |
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| 中文摘要: |
| Avadomide是处于II期临床阶段用于治疗晚期实体瘤的潜在药物，本文对其合成工艺进行了研究并对重要中间体的合成工艺进行了优化。以3-硝基邻苯二甲酰亚胺为起始原料，依次经开环、霍夫曼降解、环化、酯的氨解反应、氢氧化钯/碳加氢还原反应得到Avadomide，总收率为46.9%，产物结构经1 H NMR、13 C NMR和HRMS表征，纯度经HPLC检测为99.5%。优化后的工艺路线具有反应条件温和、后处理简单、产率高、可操作性强等特点，更适合Avadomide的工业化生产。 |
| 英文摘要: |
| Avadomide is a potential drug for the treatment of advanced solid tumors in phase II clinical trials. In this work, the synthesis technique for preparation of Avadomide was optimized and improved. Using 3-nitrophthalimide as the starting material, Avadomide was obtained by ring-cleavage, Hoffman degradation, cyclization, ester aminolysis reaction and Pd(OH)2/C hydrogenation reduction. The overall yield was 46.9% and the target compound was identified by 1HNMR, 13CNMR and HRMS, whose purity was 99.5% through HPLC test. In comparison with literature methods, this synthetic route has the advantages of mild reaction conditions, simple post-treatment, high yield and easy work-up, so it is suitable for industrial production of Avadomide. |
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