Dimethyl 3-bromo-7-azabicyclo[2.2.1]hepta-2,5-diene-2,7-dicarboxylate | 208177-19-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯啉
• 英文名称: Dimethyl 3-bromo-7-azabicyclo[2.2.1]hepta-2,5-diene-2,7-dicarboxylate
• CAS: 208177-19-9
• 化学式: C₁₀H₁₀BrNO₄
• 分子量: 288.098
• InChiKey: HWLYZFMZKJKRCP-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1
• 重原子数：
  16
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.4
• 拓扑面积：
  55.8
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  Dimethyl 3-bromo-7-azabicyclo[2.2.1]hepta-2,5-diene-2,7-dicarboxylate 在 palladium on activated charcoal 盐酸 、 palladium diacetate 、 sodium tetrahydroborate 、 氢溴酸 、 氢气 、 nickel diacetate 、 sodium cyanoborohydride 、 sodium carbonate 、 溶剂黄146 、 三苯基膦 作用下， 以 四氢呋喃 、 甲醇 、 乙醇 、 水 、 乙腈 、 苯 为溶剂， 25.0 ℃ 、275.79 kPa 条件下， 反应 71.75h， 生成 (1R,2R,3R,4S)-7-Methyl-3-phenyl-7-aza-bicyclo[2.2.1]heptane-2-carboxylic acid methyl ester
  参考文献：
  名称：

  Synthesis and Dopamine Transporter Affinity of the Four Stereoisomers of (±)-2-(Methoxycarbonyl)-7-methyl-3-phenyl-7-azabicyclo[2.2.1]heptane

  摘要：

  All four stereoisomers of (+/-)-2-(methoxycarbonyl)-7-methyl-3-phenyl-7-azabicyclo[2.2.1]heptane were synthesized and evaluated as cocaine binding site ligands at the dopamine transporter. The in vitro binding affinities (K-i) of the 7-azabicyclo[2.2.1]heptane derivatives were measured in rat caudate-putamen tissue and found, to be 100-3000;fold less potent (K-i = 5-96 mu M) than cocaine and 2 beta-(methoxycarbonyl)-3 beta-phenyltropane (2, WIN 35,065-2). Surprisingly, the 3 alpha-phenyl isomers (6c, 6d) were more potent than the 3 beta-phenyl isomers (6a, 6b). Molecular modeling studies revealed that the rigid 7-azabicyclo[2.2. I]heptane derivatives possess molecular topologies which are significantly different than the molecular topologies of the 2 beta-(methoxycarbonyl)-3-phenyltropanes.

  DOI：

  10.1021/jm9705061
• 作为产物：
  描述：

  甲基吡咯-1-羧酸酯 、 3-溴炔丙酸甲酯 反应 33.0h， 以56%的产率得到Dimethyl 3-bromo-7-azabicyclo[2.2.1]hepta-2,5-diene-2,7-dicarboxylate
  参考文献：
  名称：

  Synthesis and Dopamine Transporter Affinity of the Four Stereoisomers of (±)-2-(Methoxycarbonyl)-7-methyl-3-phenyl-7-azabicyclo[2.2.1]heptane

  摘要：

  All four stereoisomers of (+/-)-2-(methoxycarbonyl)-7-methyl-3-phenyl-7-azabicyclo[2.2.1]heptane were synthesized and evaluated as cocaine binding site ligands at the dopamine transporter. The in vitro binding affinities (K-i) of the 7-azabicyclo[2.2.1]heptane derivatives were measured in rat caudate-putamen tissue and found, to be 100-3000;fold less potent (K-i = 5-96 mu M) than cocaine and 2 beta-(methoxycarbonyl)-3 beta-phenyltropane (2, WIN 35,065-2). Surprisingly, the 3 alpha-phenyl isomers (6c, 6d) were more potent than the 3 beta-phenyl isomers (6a, 6b). Molecular modeling studies revealed that the rigid 7-azabicyclo[2.2. I]heptane derivatives possess molecular topologies which are significantly different than the molecular topologies of the 2 beta-(methoxycarbonyl)-3-phenyltropanes.

  DOI：

  10.1021/jm9705061