| 第 47 卷第 1 期 |  | Vol. 47 No. 1 | | 2017 年 2 月 | Feb 2017 |
|
所属栏目：医药及中间体
泊马度胺的合成工艺条件改进 |
| 赵胜贤1，2，严晓阳1，郑绍成1，厉 昆2，阳学文2，熊国强2，胡鸿雨1，2*
（1.浙江师范大学 行知学院，浙江 金华 321004；2.浙江普洛得邦制药有限公司，浙江 东阳 322118） |
| 摘 要：以N-叔丁氧羰基-L-谷氨酰胺（1）缩合﹑脱保护得到3-氨基哌啶- 2，6-二酮盐酸盐（3）；3-硝基邻苯二甲酸酐（4）环合得到3-硝基3-邻苯二甲酸酐（5）；3 与 5 在乙酸中回流缩合得1，3-二氧- 2-（2，6-二氧哌啶- 3-基）- 5-硝基异二氢吲哚（6）最后铁粉还原得到目标产物泊马度胺。其结构经1H NMR和MS确证。该工艺合成操作简单，反应原料价廉易得，收率较高，反应条件温和，后处理简单，无特殊设备要求，产品质量稳定。 总收率45%以上。 |
| 关键词：N-叔丁氧羰基-L-谷氨酰胺；3-硝基邻苯二甲酸酐；合成 |
| 中图分类号：O614 文献标识码：A 文章编号：1009-9212（2017）01-0050-03 |
|
| Improvement of Synthetic Technological Conditions of Pomalidomide |
| ZHAO Sheng-xian1，2, YAN Xiao-yang1, ZHENG Shao-cheng1, LI Kun2, YANG Xue-wen2, XIONG Guo-qiang2，HU Hong-yu1,2*
(1. College of Xingzhi, Zhejiang Normal University，Jinhua 321004，China; 2. Zhejiang Apeloa Tosopo Pharmaceutical Co., Ltd., Dongyang 322118, China) |
| Abstract：N-Tert-butoxycarbonyl-L-glutamine(1) was condensed and deprotected to give 3-aminopiperidine-2,6-dione hydrochloride (3); 3-nitro-3-phthalic anhydride (5) was obtained through the cyclization reaction of 3-nitrophthalic anhydride (4); 3 and 5 were refluxed in acetic acid to give 1,3-dioxo-2- (2,6-dioxopiperidine-3-yl)-5-nitroisoindoline (6). The final iron powder was used as reduce agent to give the desired product. The structure of the dopamine was confirmed by 1H-NMR. The reaction conditions were mild; the post-treatment was simple; no special equipment was required; the synthetic process was simple and the product quality was stable. The total yield of more than 45%. |
| Key words：N-tert-butoxycarbonyl-L-glutamine; 3-nitrophthalic anhydride; synthesis |
|
作者简介：赵胜贤（1970-），男，浙江绍兴人，高级工程师，博士，主要从事药物合成和晶型研究（E-mail: 2086488660@qq.com）。
|
联 系 人：胡鸿雨，博士，主要从事有机合成研究。
|
收稿日期：2017-01-16
|
|