(1R,5S)-3-methyl-7-(pyridin-3-yl)-3-azabicyclo[3.3.1]non-6-ene p-hydroxybenzoate | 1423074-47-8

• 分子结构分类: 有机化合物
• 英文名称: (1R,5S)-3-methyl-7-(pyridin-3-yl)-3-azabicyclo[3.3.1]non-6-ene p-hydroxybenzoate
• 英文别名: TC-8817 p-hydroxybenzoate
• CAS: 1423074-47-8
• 化学式: C₇H₆O₃*C₁₄H₁₈N₂
• 分子量: 352.433
• InChiKey: HTUXDCUCNRCRMF-ZVWHLABXSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.53
• 重原子数：
  26.0
• 可旋转键数：
  2.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  73.66
• 氢给体数：
  2.0
• 氢受体数：
  4.0

反应信息

• 作为产物：
  描述：

  ethyl 6,7-dibromo-3-azabicyclo[3.3.1]nonane-3-carboxylate 在 1,1'-双(二苯基膦)二茂铁 、 lithium aluminium tetrahydride 、 potassium tert-butylate 、 palladium diacetate 、 sodium carbonate 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 醋酸异丙酯 、 水 、 异丙醇 为溶剂， 反应 8.0h， 生成 (1R,5S)-3-methyl-7-(pyridin-3-yl)-3-azabicyclo[3.3.1]non-6-ene p-hydroxybenzoate
  参考文献：
  名称：

  Development of a Scalable Synthesis of a Pyridinyl-3-azabicyclononene, a Novel Nicotinic Partial Agonist

  摘要：

  The process research and development of two syntheses of a novel nicotinic partial agonist, TC-8817 ((+)-5), are described. The original Medicinal Chemistry route had multiple flaws, making it unsuitable for further development. A second approach was explored which was more amenable to optimization. The key steps were an intramolecular Lewis acid-promoted cyclization, a dibromination/elimination sequence to provide a vinyl bromide, and subsequent Suzuki coupling with 3-pyridineboronic acid. The overall yield of similar to 3-16% over nine steps was offset by the low cost of goods and ease of synthesis. A major drawback was the need for simulated moving bed chiral separation on the penultimate intermediate to afford the subsequently desired single enantiomer version. A third-generation, asymmetric variation afforded a key intermediate in good yield and enantiomeric purity, providing proof of concept for a more efficient production of the desired (+)-enantiomer.

  DOI：

  10.1021/op400002r