(1R,5S)-ethyl 7-(pyridin-3-yl)-3-azabicyclo[3.3.1]non-6-ene-3-carboxylate | 1423074-46-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 哌啶类
• 英文名称: (1R,5S)-ethyl 7-(pyridin-3-yl)-3-azabicyclo[3.3.1]non-6-ene-3-carboxylate
• 英文别名: ethyl (1R,5S)-7-pyridin-3-yl-3-azabicyclo[3.3.1]non-6-ene-3-carboxylate
• CAS: 1423074-46-7
• 化学式: C₁₆H₂₀N₂O₂
• 分子量: 272.347
• InChiKey: NAEDASQBPKYRBA-QWHCGFSZSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.9
• 重原子数：
  20
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  42.4
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  (1R,5S)-ethyl 7-(pyridin-3-yl)-3-azabicyclo[3.3.1]non-6-ene-3-carboxylate 在 lithium aluminium tetrahydride 作用下， 以 四氢呋喃 为溶剂， 生成 (1R,5S)-3-methyl-7-(pyridin-3-yl)-3-azabicyclo[3.3.1]non-6-ene
  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
• 作为产物：
  描述：

  ethyl (cyclohex-3-enylmethyl)carbamate 在 1,1'-双(二苯基膦)二茂铁 、 三氟化硼乙醚 、 potassium tert-butylate 、 溴 、 palladium diacetate 、 sodium carbonate 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 二氯甲烷 、 水 为溶剂， 反应 17.0h， 生成 (1R,5S)-ethyl 7-(pyridin-3-yl)-3-azabicyclo[3.3.1]non-6-ene-3-carboxylate
  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

文献信息

• Synthesis and Screening of Stereochemically Diverse Combinatorial Libraries of Peptide Tertiary Amides
  作者：Yu Gao、Thomas Kodadek

  DOI：10.1016/j.chembiol.2013.01.013

  日期：2013.3

  Large combinatorial libraries of N-substituted peptides would be an attractive source of protein ligands, because these compounds are known to be conformationally constrained, whereas standard peptides or peptoids are conformationally mobile. Here, we report an efficient submonomer solid-phase synthetic route to these compounds and demonstrate that it can be used to create high quality libraries. A model

  N 取代肽的大型组合文库将是蛋白质配体的有吸引力的来源，因为已知这些化合物在构象上受到限制，而标准肽或类肽在构象上是可移动的。在这里，我们报告了这些化合物的有效亚单体固相合成路线，并证明它可用于创建高质量的库。模型筛选实验和命中分析表明立体中心提供的刚性对于高亲和力结合至关重要。
• Development of a Scalable Synthesis of a Pyridinyl-3-azabicyclononene, a Novel Nicotinic Partial Agonist
  作者：Scott R. Breining、John F. Genus、J. Pike Mitchener、Timothy J. Cuthbertson、Ronald Heemstra、Matt S. Melvin、Gary M. Dull、Daniel Yohannes

  DOI：10.1021/op400002r

  日期：2013.3.15

  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.