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中国药学(英文版) ›› 2015, Vol. 24 ›› Issue (2): 133-136.DOI: 10.5246/jcps.2015.02.016

• 【简 报】 • 上一篇    

氟马西尼的有关物质B的合成

潘莉1, 温西2, 沙宇1, 朱文婷2, 程卯生1*   

  1. 1. 沈阳药科大学 基于靶点的药物设计与研究教育部重点实验室; 制药工程学院, 辽宁 沈阳 110016
    2. 保诺科技(北京)有限公司, 北京 102206
  • 收稿日期:2014-11-18 修回日期:2014-12-10 出版日期:2015-02-01 发布日期:2014-12-20
  • 通讯作者: Tel.: 86-24-23986413

Synthesis of impurity B of Flumazenil

Li Pan1, Xi Wen2, Yu Sha1, Wenting Zhu2, Maosheng Cheng1*   

  1. 1. Key Laboratory of Structure-Based Drug Design and Discovery of Ministry of Education, School of Pharmaceutical Engineering, Shenyang Pharmaceutical University, Shenyang 110016, China
    2. Bioduro Science and Technology Co. Ltd, Beijing 102206, China
  • Received:2014-11-18 Revised:2014-12-10 Online:2015-02-01 Published:2014-12-20
  • Contact: Tel.: 86-24-23986413

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摘要：

我们以7-甲氧基-4-甲基-3H-1,4-苯并二氮杂卓-2,5-(1H, 4H)–二酮为原料, 经脱甲基、苄基保护、环合和脱苄基反应合成了氟马西尼有关物质B。氟马西尼有关物质B结构经氢谱、碳谱和高分辨质谱确证, 总收率为29.3%。该发现有助于合成工艺的优化和氟马西尼的质量控制。

关键词: 氟马西尼有关物质B, 氟马西尼, 合成, 质量控制

Abstract:

We report herein the synthesis of impurity B of Flumazenil via demethylation, benzyl protection, cyclization and debenzylation from 7-methoxyl-3,4-dihydro-4-methyl-2H-1,4-benzo-diazepine-2,5(1H)-dione. The structure of impurity B of Flumazenil was confirmed by 1H NMR, 13C NMR and HRMS, and the overall yield was 29.3%. The finding will be helpful for optimizing the synthetic process and quality control of Flumazenil.

Key words: Impurity B of Flumazenil, Flumazenil, Synthesis, Quality control

中图分类号: 

Supporting:

Synthesis of 8-hydroxy Flumazenil

 

1. Analysis and identification of products

  Melting points were determined on a Büchi Melting Point B-540 apparatus and were uncorrected. 1H-NMR and 13C-NMR spectra were recorded on a Bruker ARX-300 spectrometer, using DMSO-d6 as solvent and TMS as the internal standard. Coupling constants (J) were expressed in Hz. Mass spectra were obtained on an Agilent 1100 mass spectrometer. High-resolution mass spectra (HRMS) were recorded on a Bruker microTOF-Q. Column chromatography (CC) was performed on silica gel H and analytical TLC on silica gel HF254.

 

1.1  1H-NMR spectra of 7-Benzyloxy-3, 4-dihydro-4-methyl-2H-1,4 benzodiazepine-2,5(1H)–dione 

 

 

 

 

1.2   1H-NMR and 13C-NMR spectra of 8-hydroxy Flumazenil 

 

 

 

 

 

 

 

1.3  High-resolution mass spectra of 8-hydroxy Flumazenil

 

 

 

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