(S)-3-Benzyl-7-chloro-1-isopropyl-5-phenyl-1,3-dihydro-benzo[e][1,4]diazepin-2-one | 608538-68-7

• 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: (S)-3-Benzyl-7-chloro-1-isopropyl-5-phenyl-1,3-dihydro-benzo[e][1,4]diazepin-2-one
• 英文别名: (3S)-3-benzyl-7-chloro-5-phenyl-1-propan-2-yl-3H-1,4-benzodiazepin-2-one
• CAS: 608538-68-7
• 化学式: C₂₅H₂₃ClN₂O
• 分子量: 402.923
• InChiKey: MAXLZKIQQBKXMU-QFIPXVFZSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.5
• 重原子数：
  29
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.2
• 拓扑面积：
  32.7
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  (S)-3-Benzyl-7-chloro-1-isopropyl-5-phenyl-1,3-dihydro-benzo[e][1,4]diazepin-2-one 、 碘甲烷 在 六甲基磷酰三胺 、 lithium diisopropyl amide 、 正丁基锂 作用下， 以 四氢呋喃 、 正己烷 为溶剂， 反应 3.0h， 生成 (3S)-3-benzyl-7-chloro-3-methyl-5-phenyl-1-propan-2-yl-1,4-benzodiazepin-2-one
  参考文献：
  名称：

  Enantioselective Synthesis of “Quaternary” 1,4-Benzodiazepin-2-one Scaffolds via Memory of Chirality

  摘要：

  Glycine-derived 1,4-benzodiazepine-2-ones such as diazepam are chiral by virtue of the boat-shaped conformation of the diazepine ring and exist as a racemic mixture of conformational enantiomers. However, the presence of a chiral center at C-3 of the benzodiazepine perturbs this equilibrium and preferentially stabilizes one ring conformer. We report that N-i-Pr 1,4-benzodiazepine-2-ones derived from (S)-Ala and (S)-Phe can be deprotonated and alkylated in 86-99% ee, despite the fact that the original chiral center is destroyed in the deprotonation step. We attribute this highly enantioselective alkylation to the chiral memory of the benzodiazepine ring. This protocol provides easy access to the previously unexplored "quaternary" 1,4-benzodiazepine-2-ones.

  DOI：

  10.1021/ja0365781
• 作为产物：
  描述：

  三氟甲磺酸异丙酯 、 (3S)-3-苄基-7-氯-5-苯基-1,3-二氢-1,4-苯并二氮杂-2-酮 在 sodium hydride 作用下， 以 四氢呋喃 为溶剂， 反应 0.67h， 以58%的产率得到(S)-3-Benzyl-7-chloro-1-isopropyl-5-phenyl-1,3-dihydro-benzo[e][1,4]diazepin-2-one
  参考文献：
  名称：

  Enantioselective Synthesis of “Quaternary” 1,4-Benzodiazepin-2-one Scaffolds via Memory of Chirality

  摘要：

  Glycine-derived 1,4-benzodiazepine-2-ones such as diazepam are chiral by virtue of the boat-shaped conformation of the diazepine ring and exist as a racemic mixture of conformational enantiomers. However, the presence of a chiral center at C-3 of the benzodiazepine perturbs this equilibrium and preferentially stabilizes one ring conformer. We report that N-i-Pr 1,4-benzodiazepine-2-ones derived from (S)-Ala and (S)-Phe can be deprotonated and alkylated in 86-99% ee, despite the fact that the original chiral center is destroyed in the deprotonation step. We attribute this highly enantioselective alkylation to the chiral memory of the benzodiazepine ring. This protocol provides easy access to the previously unexplored "quaternary" 1,4-benzodiazepine-2-ones.

  DOI：

  10.1021/ja0365781

文献信息

• Enantioselective Synthesis of “Quaternary” 1,4-Benzodiazepin-2-one Scaffolds via Memory of Chirality
  作者：Paul R. Carlier、Hongwu Zhao、Joe DeGuzman、Polo C.-H. Lam

  DOI：10.1021/ja0365781

  日期：2003.9.1

  Glycine-derived 1,4-benzodiazepine-2-ones such as diazepam are chiral by virtue of the boat-shaped conformation of the diazepine ring and exist as a racemic mixture of conformational enantiomers. However, the presence of a chiral center at C-3 of the benzodiazepine perturbs this equilibrium and preferentially stabilizes one ring conformer. We report that N-i-Pr 1,4-benzodiazepine-2-ones derived from (S)-Ala and (S)-Phe can be deprotonated and alkylated in 86-99% ee, despite the fact that the original chiral center is destroyed in the deprotonation step. We attribute this highly enantioselective alkylation to the chiral memory of the benzodiazepine ring. This protocol provides easy access to the previously unexplored "quaternary" 1,4-benzodiazepine-2-ones.