3-{(R)-amino[2-(2-hydroxyethyl)phenyl]methyl}indole-1-carboxylic acid tert-butyl ester | 1123754-61-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吲哚及其衍生物
• 英文名称: 3-{(R)-amino[2-(2-hydroxyethyl)phenyl]methyl}indole-1-carboxylic acid tert-butyl ester
• 英文别名: tert-butyl 3-[(R)-amino-[2-(2-hydroxyethyl)phenyl]methyl]indole-1-carboxylate
• CAS: 1123754-61-9
• 化学式: C₂₂H₂₆N₂O₃
• 分子量: 366.46
• InChiKey: VCMIVJNUQKBHKK-HXUWFJFHSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.4
• 重原子数：
  27
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.32
• 拓扑面积：
  77.5
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  3-{(R)-amino[2-(2-hydroxyethyl)phenyl]methyl}indole-1-carboxylic acid tert-butyl ester 、 叔丁基二甲基氯硅烷 在 咪唑 、 4-二甲氨基吡啶 作用下， 以 二氯甲烷 为溶剂， 以70%的产率得到3-((R)-amino{2-[2-(tert-butyldimethylsilanyloxy)ethyl]phenyl}-methyl)indole-1-carboxylic acid tert-butyl ester
  参考文献：
  名称：

  Stereoselective Synthesis of Chiral IBR2 Analogues

  摘要：

  Two stereoselective routes were developed to synthesize optically pure IBR2 analogues 1-16. The first features addition of N-Boc-3-bromoindole 26 to the sulfinamide 25, providing a 1: 1 ratio of the separable diasteroisomers 27 and 28 in good yield. In a straightforward fashion, the sulfinamides 27 and 28 were conveniently converted into the key amines 39 and 47 over 8 steps, respectively, from which a series of 3,4-dihydroisoquinolinyl IBR2 analogues 1-14 containing fluorinated and trifluoromethylated benzyl groups were prepared. Another route highlights the highly enantioselective addition of indole to the sulfonyl amide 50 with bifunctional aminothioureas 57 and 58 as catalysts. After the reaction conditions were optimized, the desired sulfonyl amides (R)-55 and (S)-55 were obtained in 99% ee and 98% ee, respectively. Acylation of (R)-55 and (S)-55 separately and subsequent allylation gave compounds 60 and 63, respectively, which were further subjected to RCM to furnish compounds 61 and 64 and, after removal of the Boc groups, the desired IBR2 analogues 15 and 16.

  DOI：

  10.1021/jo802607f
• 作为产物：
  描述：

  3-{(R)-amino[2-(2-benzyloxyethyl)phenyl]methyl}indole-1-carboxylic acid tert-butyl ester 在 盐酸 、 palladium 10% on activated carbon 、 氢气 作用下， 以 1,4-二氧六环 、 甲醇 为溶剂， 20.0 ℃ 、101.33 kPa 条件下， 反应 1.0h， 以95%的产率得到3-{(R)-amino[2-(2-hydroxyethyl)phenyl]methyl}indole-1-carboxylic acid tert-butyl ester
  参考文献：
  名称：

  Stereoselective Synthesis of Chiral IBR2 Analogues

  摘要：

  Two stereoselective routes were developed to synthesize optically pure IBR2 analogues 1-16. The first features addition of N-Boc-3-bromoindole 26 to the sulfinamide 25, providing a 1: 1 ratio of the separable diasteroisomers 27 and 28 in good yield. In a straightforward fashion, the sulfinamides 27 and 28 were conveniently converted into the key amines 39 and 47 over 8 steps, respectively, from which a series of 3,4-dihydroisoquinolinyl IBR2 analogues 1-14 containing fluorinated and trifluoromethylated benzyl groups were prepared. Another route highlights the highly enantioselective addition of indole to the sulfonyl amide 50 with bifunctional aminothioureas 57 and 58 as catalysts. After the reaction conditions were optimized, the desired sulfonyl amides (R)-55 and (S)-55 were obtained in 99% ee and 98% ee, respectively. Acylation of (R)-55 and (S)-55 separately and subsequent allylation gave compounds 60 and 63, respectively, which were further subjected to RCM to furnish compounds 61 and 64 and, after removal of the Boc groups, the desired IBR2 analogues 15 and 16.

  DOI：

  10.1021/jo802607f