10-乙酰氧基奥卡西平 | 113952-21-9

• 物质功能分类: 分析化学 - 标准品 - 药典标准品和杂质标准品
• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯氮卓类
• 中文名称: 10-乙酰氧基奥卡西平
• 中文别名: 奥卡西平杂质
• 英文名称: 5-carbamoyl-10,11-dihydro-11-oxo-5H-dibenzazepine-10-yl acetate
• 英文别名: 10-Acetyloxy Oxcarbazepine；(11-carbamoyl-5-oxo-6H-benzo[b][1]benzazepin-6-yl) acetate
• CAS: 113952-21-9
• 化学式: C₁₇H₁₄N₂O₄
• 分子量: 310.309
• InChiKey: ZKWJEEHQNGPADU-UHFFFAOYSA-N

物化性质

• 熔点：
  >187°C (Subl.)
• 溶解度：
  可溶于丙酮、氯仿、DMSO（轻微）、乙酸乙酯（轻微、加热）、甲醇

计算性质

• 辛醇/水分配系数(LogP)：
  1.7
• 重原子数：
  23
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.12
• 拓扑面积：
  89.7
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  10-乙酰氧基奥卡西平 在 吡啶 、 二异丁基氢化铝 作用下， 以 四氢呋喃 、 甲苯 为溶剂， 反应 18.5h， 生成 cis-5-carbamoyl-10,11-dihydro-5H-dibenzazepine-10,11-diyl diacetate
  参考文献：
  名称：

  的合成反式-10,11-二氢-10,11-二羟基-5- ħ二苯并[ b，˚F ]氮杂-5-甲酰胺，卡马西平的主要代谢产物

  摘要：

  从10,11-二氢-分两步制备5-氨基甲酰基-10,11-二氢-11-氧代-5 H -dibenz [ b，f ]氮杂-10-乙酸酯（6）的立体选择性研究了10-oxo-5 H -dibenz [ b，f ] azepine -5-carboxamide（4）。在使用的试剂中，发现二异丁基氢化铝（DIBAH）具有最高的反式/顺式二醇比。这允许制备卡马西平的重要的反式-二醇代谢物3（1）。

  DOI：

  10.1002/hlca.19870700730
• 作为产物：
  描述：

  奥卡西平 、 碘苯二乙酸 在 溶剂黄146 作用下， 反应 16.0h， 以27%的产率得到10-乙酰氧基奥卡西平
  参考文献：
  名称：

  Complementation of Biotransformations with Chemical C–H Oxidation: Copper-Catalyzed Oxidation of Tertiary Amines in Complex Pharmaceuticals

  摘要：

  The isolation, quantitation, and characterization of drug metabolites in biological fluids remain challenging. Rapid access to oxidized drugs could facilitate metabolite identification and enable early pharmacology and toxicity studies. Herein, we compared biotransformations to classical and new chemical C-H oxidation methods using oxcarbazepine, naproxen, and an early compound hit (phthalazine 1). These studies illustrated the low preparative efficacy of biotransformations and the inability of chemical methods to oxidize complex pharmaceuticals. We also disclose an aerobic catalytic protocole (CuI/air) to oxidize tertiary amines and benzylic CH's in drugs. The reaction tolerates a broad range of functionalities and displays a high level of chemoselectivity, which is not generally explained by the strength of the C-H bonds but by the individual structural chemotype. This study represents a first step toward establishing a chemical toolkit (chemotransformations) that can selectively oxidize C-H bonds in complex pharmaceuticals and rapidly deliver drug metabolites.

  DOI：

  10.1021/ja405471h

文献信息

• HECKENDORN, ROLAND, HELV. CHIM. ACTA, 70,(1987) N 7, 1955-1962
  作者：HECKENDORN, ROLAND

  DOI：——

  日期：——
• Complementation of Biotransformations with Chemical C–H Oxidation: Copper-Catalyzed Oxidation of Tertiary Amines in Complex Pharmaceuticals
  作者：Julien Genovino、Stephan Lütz、Dalibor Sames、B. Barry Touré

  DOI：10.1021/ja405471h

  日期：2013.8.21

  The isolation, quantitation, and characterization of drug metabolites in biological fluids remain challenging. Rapid access to oxidized drugs could facilitate metabolite identification and enable early pharmacology and toxicity studies. Herein, we compared biotransformations to classical and new chemical C-H oxidation methods using oxcarbazepine, naproxen, and an early compound hit (phthalazine 1). These studies illustrated the low preparative efficacy of biotransformations and the inability of chemical methods to oxidize complex pharmaceuticals. We also disclose an aerobic catalytic protocole (CuI/air) to oxidize tertiary amines and benzylic CH's in drugs. The reaction tolerates a broad range of functionalities and displays a high level of chemoselectivity, which is not generally explained by the strength of the C-H bonds but by the individual structural chemotype. This study represents a first step toward establishing a chemical toolkit (chemotransformations) that can selectively oxidize C-H bonds in complex pharmaceuticals and rapidly deliver drug metabolites.
• Synthesis oftrans-10,11-Dihydro-10,11-dihydroxy-5H-dibenz[b,f]azepine-5-carboxamide, a Major Metabolite of Carbamazepine
  作者：Roland Heckendorn

  DOI：10.1002/hlca.19870700730

  日期：1987.11.4

  has been studied. Among the reagents used, diisobutylaluminum hydride (DIBAH) was found to give the highest trans/cis diol ratio. This allowed the preparation of the important trans-diol metabolite 3 of carbamazepine (1).

  从10,11-二氢-分两步制备5-氨基甲酰基-10,11-二氢-11-氧代-5 H -dibenz [ b，f ]氮杂-10-乙酸酯（6）的立体选择性研究了10-oxo-5 H -dibenz [ b，f ] azepine -5-carboxamide（4）。在使用的试剂中，发现二异丁基氢化铝（DIBAH）具有最高的反式/顺式二醇比。这允许制备卡马西平的重要的反式-二醇代谢物3（1）。