1-[4-(methoxy)-1-oxobutyl]pyrrolidine | 463303-92-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯烷类
• 英文名称: 1-[4-(methoxy)-1-oxobutyl]pyrrolidine
• 英文别名: 4-Methoxy-1-pyrrolidin-1-ylbutan-1-one
• CAS: 463303-92-6
• 化学式: C₉H₁₇NO₂
• 分子量: 171.239
• InChiKey: HIMSTQUXHDPGJR-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.4
• 重原子数：
  12
• 可旋转键数：
  4
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.89
• 拓扑面积：
  29.5
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  1-[4-(methoxy)-1-oxobutyl]pyrrolidine 在 正丁基锂 、 sodium iodide 、 lithium chloride 、 锌 、 lithium diisopropyl amide 作用下， 以 四氢呋喃 、 正己烷 、 丙酮 、 甲苯 为溶剂， 反应 125.0h， 生成 6-(2-甲氧基乙基)-5,6-二氢-7H-环戊二烯并[c]吡啶-7-酮
  参考文献：
  名称：

  Conformationally Constrained Nicotines:  Polycyclic, Bridged, and Spiro-Annulated Analogues as Novel Ligands for the Nicotinic Acetylcholine Receptor

  摘要：

  A set of novel nicotine-related, conformationally constrained compounds, including tetracyclic, bridged (4), and tricyclic, spiro-annulated (5) structures, were synthesized in a straightforward manner and optically resolved in a convenient fashion with (+)- and (-)-O,O'-di-p-toluoyltartaric acids. Absolute configurations were determined by X-ray crystallography. These compounds were evaluated for their ability to displace [H-3]cytisine in a rat forebrain preparation and compared to (-)-nicotine. Three substances emerged with high affinity in the low nanomolar range. Moreover, one of these compounds ((+)-5b) showed not only high binding affinity (K-i = 4.79 nM) but also significant enantioselectivity over its antipode (K-i = 148 nM), supporting the hypothesis that conformational restraint can lead to high-affinity ligands, which are stereochemically discriminated by the nicotinic acetylcholine receptor and may feature optimum locations of the active sites of the pharmacophore.

  DOI：

  10.1021/jm020916b
• 作为产物：
  描述：

  四氢吡咯 、 4-甲氧基丁酸甲酯 在 氯化铵 作用下， 反应 4.0h， 以97%的产率得到1-[4-(methoxy)-1-oxobutyl]pyrrolidine
  参考文献：
  名称：

  Conformationally Constrained Nicotines:  Polycyclic, Bridged, and Spiro-Annulated Analogues as Novel Ligands for the Nicotinic Acetylcholine Receptor

  摘要：

  A set of novel nicotine-related, conformationally constrained compounds, including tetracyclic, bridged (4), and tricyclic, spiro-annulated (5) structures, were synthesized in a straightforward manner and optically resolved in a convenient fashion with (+)- and (-)-O,O'-di-p-toluoyltartaric acids. Absolute configurations were determined by X-ray crystallography. These compounds were evaluated for their ability to displace [H-3]cytisine in a rat forebrain preparation and compared to (-)-nicotine. Three substances emerged with high affinity in the low nanomolar range. Moreover, one of these compounds ((+)-5b) showed not only high binding affinity (K-i = 4.79 nM) but also significant enantioselectivity over its antipode (K-i = 148 nM), supporting the hypothesis that conformational restraint can lead to high-affinity ligands, which are stereochemically discriminated by the nicotinic acetylcholine receptor and may feature optimum locations of the active sites of the pharmacophore.

  DOI：

  10.1021/jm020916b

文献信息

• Catalytic Hydrogenation of Amides to Amines under Mild Conditions
  作者：Mario Stein、Bernhard Breit

  DOI：10.1002/anie.201207803

  日期：2013.2.18

  Under (not so much) pressure: A general method for the hydrogenation of tertiary and secondary amides to amines with excellent selectivity using a bimetallic Pd–Re catalyst has been developed. The reaction proceeds under low pressure and comparatively low temperature. This method provides organic chemists with a simple and reliable tool for the synthesis of amines.

  在（不是很大）压力下：已开发出一种使用双金属Pd-Re催化剂将叔酰胺和仲酰胺氢化成胺的通用方法，具有优异的选择性。反应在低压和较低温度下进行。该方法为有机化学家提供了一种简单可靠的胺合成工具。
• HEPATITIS C VIRUS INHIBITORS
  申请人：Bristol-Myers Squibb Company

  公开号：EP2499132B1

  公开（公告）日：2017-02-15
• Conformationally Constrained Nicotines:  Polycyclic, Bridged, and Spiro-Annulated Analogues as Novel Ligands for the Nicotinic Acetylcholine Receptor
  作者：Thomas Ullrich、Sylvia Krich、Dieter Binder、Kurt Mereiter、David J. Anderson、Michael D. Meyer、Michael Pyerin

  DOI：10.1021/jm020916b

  日期：2002.8.1

  A set of novel nicotine-related, conformationally constrained compounds, including tetracyclic, bridged (4), and tricyclic, spiro-annulated (5) structures, were synthesized in a straightforward manner and optically resolved in a convenient fashion with (+)- and (-)-O,O'-di-p-toluoyltartaric acids. Absolute configurations were determined by X-ray crystallography. These compounds were evaluated for their ability to displace [H-3]cytisine in a rat forebrain preparation and compared to (-)-nicotine. Three substances emerged with high affinity in the low nanomolar range. Moreover, one of these compounds ((+)-5b) showed not only high binding affinity (K-i = 4.79 nM) but also significant enantioselectivity over its antipode (K-i = 148 nM), supporting the hypothesis that conformational restraint can lead to high-affinity ligands, which are stereochemically discriminated by the nicotinic acetylcholine receptor and may feature optimum locations of the active sites of the pharmacophore.