5,6-二氢螺[环戊并[c]吡啶-7,2-吡咯烷 | 463303-91-5

• 物质功能分类: 有机原料 - 杂环化合物
• 分子结构分类: 有机化合物 - 有机氮化合物
• 中文名称: 5,6-二氢螺[环戊并[c]吡啶-7,2-吡咯烷
• 中文别名: 5,6-二氢-螺[7H-环戊烷并[C]吡啶-7,2'-吡咯烷]
• 英文名称: 5,6-dihydrospiro[cyclopenta[c]pyridine-7,2'-pyrrolidine]
• 英文别名: spiro[5,6-dihydrocyclopenta[c]pyridine-7,2'-pyrrolidine]
• CAS: 463303-91-5
• 化学式: C₁₁H₁₄N₂
• mdl: MFCD11616034
• 分子量: 174.246
• InChiKey: ZUOIZGUVVOQOLH-UHFFFAOYSA-N

物化性质

• 沸点：
  287.9±25.0℃ (760 Torr)
• 密度：
  1.14±0.1 g/cm3 (20 ºC 760 Torr)
• 闪点：
  127.9±23.2℃

计算性质

• 辛醇/水分配系数(LogP)：
  1
• 重原子数：
  13
• 可旋转键数：
  0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.545
• 拓扑面积：
  24.9
• 氢给体数：
  1
• 氢受体数：
  2

安全信息

• 海关编码：
  2933990090

反应信息

• 作为反应物：
  描述：

  苯甲酰氯 、 5,6-二氢螺[环戊并[c]吡啶-7,2-吡咯烷 在 三乙胺 作用下， 以 二氯甲烷 为溶剂， 生成 (5,6-dihydrospiro[cyclopenta[c]pyridine-7,2'-pyrrolidin]-1'-yl)(phenyl)methanone
  参考文献：
  名称：

  极性杂苄基 C(sp3)–H 氯化途径实现芳香族氮杂环的高效多样化

  摘要：

  苄基 C-H 键的位点选择性自由基反应现在是 C(sp 3 –H) 官能化和交叉偶联的高效方法。然而，现有方法通常对药物和农用化学品中突出的烷基取代吡啶和相关芳香杂环中的杂苄基 C-H 键无效。在这里，我们报告了新的合成方法，利用极性而不是自由基反应途径来实现2-和4-烷基取代的吡啶和其他杂环的选择性杂苄基C-H氯化。用三氟甲磺酰氯催化活化底物促进烯胺互变异构体的形成，该互变异构体容易与亲电氯化试剂反应。所得杂苄基氯无需分离或纯化即可用于亲核偶联反应。这种氯化多样化序列提供了一种有效的策略，可实现与脂肪胺和多种唑类以及其他偶联伙伴的杂苄基 C-H 交叉偶联。

  DOI：

  10.1021/jacs.3c05822
• 作为产物：
  描述：

  3-bromopyridinium ethylformate chloride 在 盐酸 、 正丁基锂 、 sodium hydride 、 lithium chloride 、 锌 作用下， 以 四氢呋喃 、 正己烷 、 甲苯 为溶剂， 反应 85.5h， 生成 5,6-二氢螺[环戊并[c]吡啶-7,2-吡咯烷
  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

• 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.
• Polar Heterobenzylic C(sp³)–H Chlorination Pathway Enabling Efficient Diversification of Aromatic Nitrogen Heterocycles
  作者：Soham Maity、Marco A. Lopez、Desiree M. Bates、Shishi Lin、Shane W. Krska、Shannon S. Stahl

  DOI：10.1021/jacs.3c05822

  日期：2023.9.13

  leverage polar, rather than radical, reaction pathways to enable the selective heterobenzylic C–H chlorination of 2- and 4-alkyl-substituted pyridines and other heterocycles. Catalytic activation of the substrate with trifluoromethanesulfonyl chloride promotes the formation of enamine tautomers that react readily with electrophilic chlorination reagents. The resulting heterobenzyl chlorides can be used

  苄基 C-H 键的位点选择性自由基反应现在是 C(sp 3 –H) 官能化和交叉偶联的高效方法。然而，现有方法通常对药物和农用化学品中突出的烷基取代吡啶和相关芳香杂环中的杂苄基 C-H 键无效。在这里，我们报告了新的合成方法，利用极性而不是自由基反应途径来实现2-和4-烷基取代的吡啶和其他杂环的选择性杂苄基C-H氯化。用三氟甲磺酰氯催化活化底物促进烯胺互变异构体的形成，该互变异构体容易与亲电氯化试剂反应。所得杂苄基氯无需分离或纯化即可用于亲核偶联反应。这种氯化多样化序列提供了一种有效的策略，可实现与脂肪胺和多种唑类以及其他偶联伙伴的杂苄基 C-H 交叉偶联。