6-(2-chlorophenyl)-1-(1,1-dimethylethyl)-8-fluoro-4H-imidazo<1,5-a><1,4>benzodiazepine-3-carboxamide | 149951-34-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯二氮卓类
• 英文名称: 6-(2-chlorophenyl)-1-(1,1-dimethylethyl)-8-fluoro-4H-imidazo<1,5-a><1,4>benzodiazepine-3-carboxamide
• 英文别名: -(-)-6-(2-chlorophenyl)-1-(1,1-dimethylethyl)-8-fluoro-4H-imidazo<1,5-a><1,4>benzodiazepine-3-carboxamide；-(-)-6-(2-chlorophenyl)-1-(1,1-dimethylethyl)-8-fluoro-4H-imidazo<1,5-a><1,4>benzodiazepine-3-carboxamide；1-tert-butyl-6-(2-chlorophenyl)-8-fluoro-4H-imidazo[1,5-a][1,4]benzodiazepine-3-carboxamide
• CAS: 149951-34-8
• 化学式: C₂₂H₂₀ClFN₄O
• 分子量: 410.878
• InChiKey: HENCWLQNOIGYEA-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.4
• 重原子数：
  29
• 可旋转键数：
  3
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.23
• 拓扑面积：
  73.3
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  6-(2-chlorophenyl)-1-(1,1-dimethylethyl)-8-fluoro-4H-imidazo<1,5-a><1,4>benzodiazepine-3-carboxamide 在 sodium cyanoborohydride 、 溶剂黄146 作用下， 以 甲醇 为溶剂， 反应 4.0h， 以89%的产率得到6-(2-chlorophenyl)-8-fluoro-5,6-dihydro-1-(1,1-dimethylethyl)-4H-imidazo<1,5-a><1,4>benzodiazepine-3-carboxamide
  参考文献：
  名称：

  Atropisomers of 1,4-benzodiazepines. 2. Synthesis and resolution of imidazo[1,5-a][1,4]benzodiazepines

  摘要：

  The resolution of the 1-tert-butylimidazo[1,5-a][1,4]benzodiazepines 12, 25, and 31 is described. These compounds do not contain a center of asymmetry but exist as conformational isomers due to the presence of a chiral plane. The resolution was carried out by the following sequence of reactions: (1) reduction of the 5,6-imine bond in 12, 25, and 31 to give the dihydro derivatives 13, 27, and 33, respectively, which contain two elements of asymmetry, (2) resolution of 13, 27, and 33 employing optically active acids, and (3) oxidation of the enantiomers of 13 (13a, 13b), 27 (27a, 27b), and 33 (33a, 33b) to reintroduce the 5,6-imine bond to give the enantiomers of 12 (12a, 12b), 25 (25a, 25b), and 31 (31a, 31b), respectively. As a consequence of the oxidation, the center of asymmetry is lost while the conformational integrity is maintained. The absolute configurations of 12b, 25b, and 31a were determined by single crystal X-ray analysis. Based on the biological activity of enantiomeric pairs, the [R] configuration is required for recognition at the benzodiazepine receptor complex.

  DOI：

  10.1021/jo00064a014
• 作为产物：
  描述：

  6-(2-chlorophenyl)-1-(1,1-dimethylethyl)-8-fluoro-4H-imidazo<1,5-a><1,4>benzodiazepine-3-carboxylic acid ethyl ester 在 氢氧化钾 、 五氯化磷 、 氨 作用下， 以 甲醇 、 二氯甲烷 、 水 为溶剂， 反应 7.0h， 生成 6-(2-chlorophenyl)-1-(1,1-dimethylethyl)-8-fluoro-4H-imidazo<1,5-a><1,4>benzodiazepine-3-carboxamide
  参考文献：
  名称：

  Atropisomers of 1,4-benzodiazepines. 2. Synthesis and resolution of imidazo[1,5-a][1,4]benzodiazepines

  摘要：

  The resolution of the 1-tert-butylimidazo[1,5-a][1,4]benzodiazepines 12, 25, and 31 is described. These compounds do not contain a center of asymmetry but exist as conformational isomers due to the presence of a chiral plane. The resolution was carried out by the following sequence of reactions: (1) reduction of the 5,6-imine bond in 12, 25, and 31 to give the dihydro derivatives 13, 27, and 33, respectively, which contain two elements of asymmetry, (2) resolution of 13, 27, and 33 employing optically active acids, and (3) oxidation of the enantiomers of 13 (13a, 13b), 27 (27a, 27b), and 33 (33a, 33b) to reintroduce the 5,6-imine bond to give the enantiomers of 12 (12a, 12b), 25 (25a, 25b), and 31 (31a, 31b), respectively. As a consequence of the oxidation, the center of asymmetry is lost while the conformational integrity is maintained. The absolute configurations of 12b, 25b, and 31a were determined by single crystal X-ray analysis. Based on the biological activity of enantiomeric pairs, the [R] configuration is required for recognition at the benzodiazepine receptor complex.

  DOI：

  10.1021/jo00064a014