7-chloro-5-(2-fluorophenyl)-alpha-hydroxyimino-3H-1,4-benzodiazepine-2-acetic acid ethyl ester | 77132-89-9

• 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: 7-chloro-5-(2-fluorophenyl)-alpha-hydroxyimino-3H-1,4-benzodiazepine-2-acetic acid ethyl ester
• 英文别名: 7-Chloro-5-(2-fluorophenyl)-alpha-hydroxyimino-3H-1,4-benzodiazepine-2-acetic acid ethyl ester；ethyl 2-[7-chloro-5-(2-fluorophenyl)-3H-1,4-benzodiazepin-2-yl]-2-hydroxyiminoacetate
• CAS: 77132-89-9
• 化学式: C₁₉H₁₅ClFN₃O₃
• 分子量: 387.798
• InChiKey: RJPUXBBFXMYRFL-UHFFFAOYSA-N

物化性质

• 沸点：
  547.0±60.0 °C(Predicted)
• 密度：
  1.38±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.7
• 重原子数：
  27
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.16
• 拓扑面积：
  83.6
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  7-chloro-5-(2-fluorophenyl)-alpha-hydroxyimino-3H-1,4-benzodiazepine-2-acetic acid ethyl ester 在 镍 氢氧化钾 、 sodium cyanoborohydride 、 溶剂黄146 作用下， 以 四氢呋喃 、 甲醇 、 乙醇 、 水 、 异丙醇 为溶剂， 25.0 ℃ 、101.33 kPa 条件下， 反应 15.5h， 生成 (6S)--8-chloro-1-(1,1-dimethylethyl)-5,6-dihydro-6-(2-fluorophenyl)-4H-imidazo<1,5-a><1,4>benzodiazepine, salt with (-)-7,7-dimethyl-2-oxobicyclo<2.2.1>heptane-1-methylenesulfonic acid
  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：

  7-chloro-5-(2-fluorophenyl)-1,3-dihydro-2H-1,4-benzodiazepine-2-ylideneacetic acid ethyl ester 4-oxide 在 溶剂黄146 、 sodium nitrite 、 三氯化磷 作用下， 以 二氯甲烷 为溶剂， 反应 3.25h， 生成 7-chloro-5-(2-fluorophenyl)-alpha-hydroxyimino-3H-1,4-benzodiazepine-2-acetic acid ethyl ester
  参考文献：
  名称：

  喹唑啉和1,4-苯并二氮杂pine。XCV †。2-碳甲基喹唑啉与碳环扩环合成1,4-苯并二氮杂pine

  摘要：

  通过使2-氯甲基喹唑啉3-氧化物与稳定的碳负离子反应，获得在2-位带有碳取代基的1，4-苯并二氮杂s。成功应用了乙酸烷基酯，N，N-二取代的乙酰胺，乙腈，二甲基砜，N，N-二甲基甲磺酰胺和2-甲基吡啶的碳负离子。一些2-碳取代的1,4-苯并二氮杂卓向咪唑并[1,5- a ] [1,4]苯并二氮杂卓和[1,2,5]恶二嗪[5,4- a ] [1,4 ]的转化描述了]苯并二氮杂s。

  DOI：

  10.1002/jhet.5570230509

文献信息

• Intermediates for the production of imidazobenzodiazepines
  申请人：Hoffmann-La Roche Inc.

  公开号：US04238610A1

  公开（公告）日：1980-12-09

  Novel intermediates of the formula ##STR1## wherein X and Y are hydrogen, halogen or trifluoromethyl and R.sub.1 is hydrogen or lower alkyl are presented. Also disclosed is a process leading to the intermediates and their conversion to imidazobenzodiazepines, compounds of pharmacological activity.

  本发明涉及一种新的中间体，其化学式为 ##STR1## 其中X和Y为氢、卤素或三氟甲基，R.sub.1为氢或低碳基。此外，还揭示了一种制备该中间体的过程以及将其转化为咪唑苯并二氮平，具有药理活性的化合物。
• Quinazolines and 1,4-benzodiazepines. XCV. Synthesis of 1,4-benzodiazepines by ring expansion of 2-chloromethylquinazolines with carbanions
  作者：A. Walser、T. Flynn、C. Mason、R. Ian Fryer

  DOI：10.1002/jhet.5570230509

  日期：1986.9

  1,4-Benzodiazepines bearing a carbon substituent at the 2-position were obtained by reaction of 2-chloromethylquinazoline 3-oxides with stabilized carbanions. The carbanions of alkyl acetates, N,N-disubstituted acetamides, acetonitrile, dimethylsulfone, N,N-dimethyl methanesulfonamide and 2-methylpyridine were successfully applied. The conversion of some of the 2-carbon substituted 1,4-benzodiazepines

  通过使2-氯甲基喹唑啉3-氧化物与稳定的碳负离子反应，获得在2-位带有碳取代基的1，4-苯并二氮杂s。成功应用了乙酸烷基酯，N，N-二取代的乙酰胺，乙腈，二甲基砜，N，N-二甲基甲磺酰胺和2-甲基吡啶的碳负离子。一些2-碳取代的1,4-苯并二氮杂卓向咪唑并[1,5- a ] [1,4]苯并二氮杂卓和[1,2,5]恶二嗪[5,4- a ] [1,4 ]的转化描述了]苯并二氮杂s。
• Atropisomers of 1,4-benzodiazepines. 2. Synthesis and resolution of imidazo[1,5-a][1,4]benzodiazepines
  作者：Norman W. Gilman、Perry Rosen、James V. Earley、Charles M. Cook、John F. Blount、Louis J. Todaro

  DOI：10.1021/jo00064a014

  日期：1993.6

  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.