[1]李贝贝,邱飞,王立强.奥拉帕尼的合成工艺改进[J].华侨大学学报(自然科学版),2017,38(4):521-524.[doi:10.11830/ISSN.1000-5013.201704014]
　LI Beibei,QIU Fei,WANG Liqiang.Improved Synthesis of Olaparib[J].Journal of Huaqiao University(Natural Science),2017,38(4):521-524.[doi:10.11830/ISSN.1000-5013.201704014]
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奥拉帕尼的合成工艺改进()
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《华侨大学学报（自然科学版）》[ISSN:1000-5013/CN:35-1079/N]

卷:
第38卷
期数:
2017年第4期
页码:
521-524
栏目:
出版日期:
2017-07-10

文章信息/Info

Title:
Improved Synthesis of Olaparib
文章编号:
1000-5013(2017)04-0521-04
作者:
李贝贝1; 2;  邱飞1; 2;  王立强1; 2; 3
1. 华侨大学 分子药物研究院, 福建 泉州 362021;2. 华侨大学 生物医学学院, 福建 泉州 362021;3. 广州优米健医药科技有限公司, 广东 广州 510050
Author(s):
LI Beibei1; 2;  QIU Fei1; 2;  WANG Liqiang1; 2; 3
1.Institutes of Molecular Medicine, Huaqiao University, Quanzhou 362021, China; 2. School of Biomedical Science, Huaqiao University, Quanzhou 362021, China; 3. Guangzhou Youmijian Pharmaceutical Technology Company Limited, Guangzhou 510050, China
关键词:
磷叶立德;  邻羧基苯甲醛;  亚磷酸二甲酯;  Wittig-Horner反应;  酰化反应
Keywords:
phosphorus ylide;  dimethyl phosphonate;  2-carboxybenzaldehydereacting;  Wittig-Horner reaction;  acylation
分类号:
R914.5
DOI:
10.11830/ISSN.1000-5013.201704014
文献标志码:
A
摘要:
对奥拉帕尼的合成工艺进行改进,采用邻羧基苯甲醛与亚磷酸二甲酯反应得到磷叶立德,然后,与2-氟-5-甲酰基苯腈进行Wittig-Horner反应、水解和环合反应制得关键中间体化合物6.化合物6制成酰氯后与4-环丙基羰基哌嗪反应制得奥拉帕尼,产物结构经高分辨质谱,核磁共振氢谱和碳谱等确证.对磷叶立德的制备、Wittig-Horner反应和酰化反应等进行了工艺优化.结果表明:5步反应总收率为38.9%(以邻羧基苯甲醛计),比文献报道略高;改进后的工艺降低反应成本,缩短反应时间,简化操作.
Abstract:
The synthesis process of olaparib was improved. Olaparib was synthesized including 2-carboxybenzaldehydereacting with dimethyl phosphonate to get phosphorus ylide, Wittig-Horner reaction with 2-fluo-ro-5-cyanobenzaldehyde, hydrolyzation, cyclization to get the key intermediate 6, chloroformylation and reaction with 4-cyclopropyl carbonyl piperazine. The structure was confirmed by HRMS, 1H NMR, and 13C NMR. The process was improved including the preparation of phosphorus ylide, Wittig-Horner reaction and acylation. The result showed that the yield of the 5 steps was 38.9%(2-carboxybenzaldehyde as a benchmark)which is a little higher than the yield reported in literature; the improved process has lowered the cost, shortened the reaction time and simplified the operation.

参考文献/References:

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备注/Memo

备注/Memo:
收稿日期: 2016-01-20
通信作者: 邱飞(1978-),男,讲师,博士,主要从事新药开发领域的研究.E-mail:qiufei@hqu.edu.cn.
基金项目: 福建省自然科学基金资助项目(2015J01342); 华侨大学研究生科研创新能力培育计划项目(1400216004)
更新日期/Last Update: 2017-07-20