(3S)-7-氯-3-甲基-5-苯基-1,3-二氢-1,4-苯并二氮杂-2-酮 | 39200-48-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯二氮卓类
• 中文名称: (3S)-7-氯-3-甲基-5-苯基-1,3-二氢-1,4-苯并二氮杂-2-酮
• 英文名称: (S)-7-chloro-1,3-dihydro-3-methyl-5-phenyl-2H-1,4-benzodiazepine-2-one
• 英文别名: 7-chloro-3-methyl-5-phenyl-1,3-dihydro-benzo[e][1,4]diazepin-2-one；2H-1,4-Benzodiazepin-2-one, 1,3-dihydro-7-chloro-3-methyl-5-phenyl-, (S)-；(3S)-7-chloro-3-methyl-5-phenyl-1,3-dihydro-1,4-benzodiazepin-2-one
• CAS: 39200-48-1
• 化学式: C₁₆H₁₃ClN₂O
• 分子量: 284.745
• InChiKey: SATGIBNNISQKBG-JTQLQIEISA-N

物化性质

• 熔点：
  200 °C
• 沸点：
  453.7±45.0 °C(Predicted)
• 密度：
  1.29±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  20
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.12
• 拓扑面积：
  41.5
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  (3S)-7-氯-3-甲基-5-苯基-1,3-二氢-1,4-苯并二氮杂-2-酮 在 六甲基磷酰三胺 、 sodium hydride 、 lithium diisopropyl amide 作用下， 以 四氢呋喃 、 正己烷 为溶剂， 反应 4.17h， 生成 3-benzyl-7-chloro-1,3-dimethyl-5-phenyl-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：

  2-N-(N'-Boc-L-alanyl)amino-5-chlorobenzophenone 在 盐酸 、 sodium hydroxide 作用下， 以 甲醇 、 氯仿 、 水 为溶剂， 反应 10.0h， 生成 (3S)-7-氯-3-甲基-5-苯基-1,3-二氢-1,4-苯并二氮杂-2-酮
  参考文献：
  名称：

  Discrimination between Enantiomers of Structurally Related Molecules:  Separation of Benzodiazepines by Molecularly Imprinted Polymers

  摘要：

  Molecular imprinting has been used to create synthetic receptor sites for a series of chiral benzodiazepines. A detailed HPLC analysis of binding properties using molecularly imprinted polymers (MIPs) as the stationary phase showed that binding, as measured by chromatographic retention, shows significant dependence on the chiral match or mismatch. In addition, the shape and spatial orientation of functionality of the imprinted binding site is also critical for recognition. Imprinted polymers, therefore, are not only able to discriminate between enantiomers of the imprinted molecule, they also demonstrate an ability to discriminate between a wide range of enantiomers of structurally related molecules that have not been imprinted. The ability of MIPs to discriminate between enantiomers of molecules in favor of the imprinted absolute configuration, even as the structural homology between the enantiomers and the original template decreases, indicates that the synthetic benzodiazepine receptors may serve as crude mimics of the natural receptor.

  DOI：

  10.1021/ja9926313

文献信息

• Enantioselective Synthesis of Diversely Substituted Quaternary 1,4-Benzodiazepin-2-ones and 1,4-Benzodiazepine-2,5-diones
  作者：Paul R. Carlier、Hongwu Zhao、Stephanie L. MacQuarrie-Hunter、Joseph C. DeGuzman、Danny C. Hsu

  DOI：10.1021/ja0640142

  日期：2006.11.1

  Benzodiazepines are privileged scaffolds in medicinal chemistry, but enantiopure examples containing quaternary stereogenic centers are extremely rare. We demonstrate that installation of the di(p-anisyl)methyl (DAM) group at N1 of 1,4-benzodiazepin-2-ones and 1,4-benzodiazepine-2,5-diones derived from enantiopure proteinogenic amino acids allows retentive replacement of the C3-proton via a deprotonation/trapping

  苯二氮卓类药物是药物化学中的特殊支架，但含有四元立体中心的对映体纯的例子极为罕见。我们证明了在源自对映体纯蛋白氨基酸的 1,4-苯二氮卓-2-酮和 1,4-苯二氮卓-2,5-二酮的 N1 处安装二（对茴香基）甲基 (DAM) 基团允许保留替换C3 质子通过去质子化/捕获协议。多种碳和氮亲电子试剂在该反应中发挥良好作用，为相应的季苯二氮卓类化合物提供了出色的对映选择性。一对非对映体 1,4-苯二氮卓-2,5-二酮的去质子化/捕获实验为构象手性在这些对映选择性反应中的关键作用提供了证据。DAM 基团的酸性去除速度快且产率高，并且可以在 N-Boc 吲哚存在下选择性地进行。因此，现在可以完成具有不同 N1 功能的季苯二氮卓类化合物的合成。
• Memory of chirality trapping of low inversion barrier 1,4-benzodiazepin-2-one enolates
  作者：Paul R. Carlier、Polo C.-H. Lam、Joseph C. DeGuzman、Hongwu Zhao

  DOI：10.1016/j.tetasy.2005.08.017

  日期：2005.9

  We have previously demonstrated that chiral, enantiopure 3-substituted 1,4-benzodiazepin-2-ones undergo retentive deprotonation/trapping at −78 °C, if the N1-substituent is sufficiently large (e.g., i-Pr). Stereocontrol in this reaction is attributed to the formation of an enantiopure, conformationally chiral enolate; at −78 °C a large N1 substituent (e.g., i-Pr) is needed to impart a sufficient barrier

  先前我们已经证明，如果N1-取代基足够大（例如，i -Pr），则手性，对映体纯的3-取代的1,4-苯并二氮杂-2-酮会在-78°C下发生保持性去质子化/捕获。该反应中的立体控制归因于对映纯的，构象性的手性烯醇盐的形成。在-78°C下，需要一个大的N1取代基（例如i- Pr）来赋予烯醇外消旋作用足够的屏障。在本文中，我们报告了在低反型势垒1,4-苯并二氮杂-2-酮具有较小N1取代基的去质子化/烷基化中实现高对映体过量的策略。
• Regioselective Synthesis of New Triheterocyclic Compounds from 1,4-Benzodiazepine
  作者：R. Benelbaghdadi、A. Hasnaoui、J.-P. Lavergne、M. Giorgi、M. Pierrot

  DOI：10.1080/00397919809458703

  日期：1998.11

  Abstract As part of our program on the synthesis of new heterocyclic compounds, we report here a one-step synthesis of [1,2,4]triazolo[4,3-d][1,4]benzodiazepine 3 and [1,2,4]oxadiazolo[4,5-d][1,4]benzodiazepine 5 by 1,3-dipolar cycloaddition of nitrilimines and nitrile oxides with 1,4-benzodiazepines 1.

  摘要 作为我们合成新杂环化合物计划的一部分，我们在此报告了 [1,2,4] 三唑并 [4,3-d][1,4] 苯二氮卓 3 和 [1,2 ,4]恶二唑并[4,5-d][1,4]苯二氮卓5通过腈亚胺和腈氧化物与1,4-苯二氮卓1的1,3-偶极环加成反应。
• Chiral 1,4-benzodiazepines. XII. Conformation in a solution of 7-chloro-5-phenyl-3(S)methyl-1,3-dihydro-2<i>H</i>-1,4-benzodiazepine
  作者：E. Decorte、R. Toso、T. Fajdiga、G. Comisso、F. Moimas、A. Sega、V. Sunjić、A. Lisini

  DOI：10.1002/jhet.5570200534

  日期：1983.9

  Deuterium labeled congeners of 7-chloro-5-phenyl-3(S)-methyl-1,3-dihydro-2H-1,4-benzodiazepine (8), i.e., compounds 9 and 16-18 were prepared and their lis-nmr spectra run. For computational studies compounds 9 and 16 were chosen. The results of lis measurements revealed that 16 is present in more than 97% in the boat-like conformation I (Scheme 3).

  7-氯-5-苯基-3-（S）的氘标记的同源物-甲基-1,3-二氢-2- ħ -1,4-苯并二氮杂（8），即，化合物9和16-18中制备和它们的LIS -nmr光谱运行。为了进行计算研究，选择了化合物9和16。lis测量的结果表明，在舟状构象I中，有16种以超过97％的比例存在（方案3）。
• Gratton; Decorte; Moimas, Farmaco, Edizione Scientifica, 1985, vol. 40, # 3, p. 209 - 217
  作者：Gratton、Decorte、Moimas、Angeli、Sunjic

  DOI：——

  日期：——