第 47 卷第 1 期 | | Vol. 47 No. 1 | 2017 年 2 月 | Feb 2017 |
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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 |
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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 |
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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)。
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联 系 人:胡鸿雨,博士,主要从事有机合成研究。
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收稿日期:2017-01-16
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