2-methoxy-5-(pyrrolidin-2-yl)pyridine | 185510-44-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡啶及其衍生物
• 英文名称: 2-methoxy-5-(pyrrolidin-2-yl)pyridine
• 英文别名: 6-methoxy-nornicotine；2-Methoxy-5-(2-pyrrolidinyl)pyridine；2-methoxy-5-pyrrolidin-2-ylpyridine
• CAS: 185510-44-5
• 化学式: C₁₀H₁₄N₂O
• 分子量: 178.234
• InChiKey: UPHRHXBEESDMCP-UHFFFAOYSA-N

物化性质

• 沸点：
  283.1±40.0 °C(Predicted)
• 密度：
  1.072±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.5
• 重原子数：
  13
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  34.2
• 氢给体数：
  1
• 氢受体数：
  3

安全信息

• 危险性防范说明：
  P261,P305+P351+P338
• 危险性描述：
  H302,H315,H319,H335

反应信息

• 作为反应物：
  描述：

  2-methoxy-5-(pyrrolidin-2-yl)pyridine 在 盐酸 、 sodium acetate 、 sodium cyanoborohydride 作用下， 以 乙醚 、 水 为溶剂， 反应 0.25h， 生成
  参考文献：
  名称：

  Pyrrolidine-modified and 6-substituted analogs of nicotine: A structure—affinity investigation

  摘要：

  Because the structural requirements for the binding of nicotine to central nicotine receptors remain largely uninvestigated, we undertook a systematic investigation of pyrrolidine ring-opened analogs. This led to a subsequent investigation of related conformationally restricted derivatives of these analogs. The results are reported relative to the binding of several well-known and widely used nicotine receptor ligands. Although none of the ring-opened analogs binds with higher affinity than (-)nicotine (K-i = 2.3 nM), 3-(N-methyl-N-ethylaminomethyl)pyridine (12a; K-i = 28 nM) binds with significant affinity. A conformationally restricted analog of 12a, N-methyl [2,7]naphthyridine 30b (K-i = 18 nM), binds with similar affinity. 6-Substitution of 12a and racemic nicotine seems to be tolerated when the substituent is halogen or methyl. In functional studies (hypolocomotion and antinociception in mice; stimulus generalization in nicotine-trained rats) 30b retains nicotine-like properties. Several of the 6-substituted compounds were 2 to 20 times more potent than (+/-)nicotine. Although the intact pyrrolidine ring of nicotine appears important for optimal affinity, its pre presence is not an absolute requirement for activity, and 6-position substitution of the pyridine nucleus can influence both binding and functional activity.

  DOI：

  10.1016/s0223-5234(97)89850-9
• 作为产物：
  描述：

  5-(1-benzylpyrrolidin-2-yl)-2-methoxypyridine 在 palladium 10% on activated carbon 作用下， 以 乙醇 为溶剂， 55.0 ℃ 、101.33 kPa 条件下， 反应 2.0h， 以75%的产率得到2-methoxy-5-(pyrrolidin-2-yl)pyridine
  参考文献：
  名称：

  微波辅助铱催化合成烟碱和烟碱衍生物

  摘要：

  摘要 通过三步序列合成了各种功能化的尼古丁和金刚烷类似物，该步骤利用微波辅助的铱催化的1,4-和1,5-二醇的N杂环化来构建吡咯烷和哌啶环系统。微波辅助的N-杂环化提供了高产率（50-75％）的尼古丁和金刚烷衍生物，总产率为30-50％。 通过三步序列合成了各种功能化的尼古丁和金刚烷类似物，该步骤利用微波辅助的铱催化的1,4-和1,5-二醇的N杂环化来构建吡咯烷和哌啶环系统。微波辅助的N-杂环化提供了高产率（50-75％）的尼古丁和金刚烷衍生物，总产率为30-50％。

  DOI：

  10.1055/s-0032-1316859

文献信息

• Synthesis, receptor binding and QSAR studies on 6-substituted nicotine derivatives as cholinergic ligands
  作者：M DUKAT、M DOWD、M DAMAJ、B MARTIN、M ELZAHABI、R GLENNON

  DOI：10.1016/s0223-5234(99)80038-5

  日期：1999.1
• Pyrrolidine-modified and 6-substituted analogs of nicotine: A structure—affinity investigation
  作者：M Dukat、W Fiedler、D Dumas、I Damaj、BR Martin、JA Rosecrans、JR James、RA Glennon

  DOI：10.1016/s0223-5234(97)89850-9

  日期：1996.1

  Because the structural requirements for the binding of nicotine to central nicotine receptors remain largely uninvestigated, we undertook a systematic investigation of pyrrolidine ring-opened analogs. This led to a subsequent investigation of related conformationally restricted derivatives of these analogs. The results are reported relative to the binding of several well-known and widely used nicotine receptor ligands. Although none of the ring-opened analogs binds with higher affinity than (-)nicotine (K-i = 2.3 nM), 3-(N-methyl-N-ethylaminomethyl)pyridine (12a; K-i = 28 nM) binds with significant affinity. A conformationally restricted analog of 12a, N-methyl [2,7]naphthyridine 30b (K-i = 18 nM), binds with similar affinity. 6-Substitution of 12a and racemic nicotine seems to be tolerated when the substituent is halogen or methyl. In functional studies (hypolocomotion and antinociception in mice; stimulus generalization in nicotine-trained rats) 30b retains nicotine-like properties. Several of the 6-substituted compounds were 2 to 20 times more potent than (+/-)nicotine. Although the intact pyrrolidine ring of nicotine appears important for optimal affinity, its pre presence is not an absolute requirement for activity, and 6-position substitution of the pyridine nucleus can influence both binding and functional activity.
• Microwave-Assisted Iridium-Catalyzed Synthesis of Nicotine and Anabasine Derivatives
  作者：Mark Trudell、Tushar Apsunde

  DOI：10.1055/s-0032-1316859

  日期：——

  Abstract Various functionalized nicotine and anabasine analogues are synthesized via a three-step sequence that exploits a microwave-assisted iridium-catalyzed N-heterocyclization of 1,4- and 1,5-diols for the construction of the pyrrolidine and piperidine ring systems. The microwave-assisted N-heterocyclization furnishes derivatives of nicotine and anabasine in good yields (50–75%) with overall yields

  摘要 通过三步序列合成了各种功能化的尼古丁和金刚烷类似物，该步骤利用微波辅助的铱催化的1,4-和1,5-二醇的N杂环化来构建吡咯烷和哌啶环系统。微波辅助的N-杂环化提供了高产率（50-75％）的尼古丁和金刚烷衍生物，总产率为30-50％。 通过三步序列合成了各种功能化的尼古丁和金刚烷类似物，该步骤利用微波辅助的铱催化的1,4-和1,5-二醇的N杂环化来构建吡咯烷和哌啶环系统。微波辅助的N-杂环化提供了高产率（50-75％）的尼古丁和金刚烷衍生物，总产率为30-50％。