tert-butyl (3S,5S)-3-[3,3-dimethyl-1-(o-tolyl)-6-oxo-2H-pyridin-4-yl]-5-{[(1R)-1-(5-fluoro-2-pyridyl)-3-methylbutyl]carbamoyl}piperidine-1-carboxylate | 1620523-77-4

• 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: tert-butyl (3S,5S)-3-[3,3-dimethyl-1-(o-tolyl)-6-oxo-2H-pyridin-4-yl]-5-{[(1R)-1-(5-fluoro-2-pyridyl)-3-methylbutyl]carbamoyl}piperidine-1-carboxylate
• CAS: 1620523-77-4
• 化学式: C₃₅H₄₇FN₄O₄
• 分子量: 606.781
• InChiKey: PIYHAPHIGKXQEJ-BEYSDYMESA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.61
• 重原子数：
  44.0
• 可旋转键数：
  7.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.54
• 拓扑面积：
  91.84
• 氢给体数：
  1.0
• 氢受体数：
  5.0

反应信息

• 作为反应物：
  描述：

  tert-butyl (3S,5S)-3-[3,3-dimethyl-1-(o-tolyl)-6-oxo-2H-pyridin-4-yl]-5-{[(1R)-1-(5-fluoro-2-pyridyl)-3-methylbutyl]carbamoyl}piperidine-1-carboxylate 、 富马酸 在 三氟乙酸 作用下， 以 二氯甲烷 、 甲醇 为溶剂， 反应 0.75h， 以0.69 g的产率得到(3S,5S)-5-[3,3-dimethyl-1-(o-tolyl)-6-oxo-2H-pyridin-4-yl]-N-[(1R)-1-(5-fluoro-2-pyridyl)-3-methylbutyl]piperidine-3-carboxamide fumarate
  参考文献：
  名称：

  An Efficient Synthesis of (3S,5S)-5-[3,3-Dimethyl-1-(o-tolyl)-6-oxo-2H-pyridin-4-yl]piperidine-3-carboxamide as Potent Renin Inhibitor

  摘要：

  We report synthesis and biological evaluation of (3S,5S)-5-[3,3-dimethyl-1-(o-tolyl)-6-oxo-2H-pyridin-4-yl]piperidine-3-carboxamide as renin inhibitor. This effective synthetic route involves a zinc mediated Barbier reaction and an intramolecular Horner-Wadsworth-Emmons reaction of sterically hindered ketone as key reactions. The prepared compound 4 exhibited both potent renin inhibitory activity and significant in vivo efficacy in furosemide pretreated cynomolgus monkeys.

  DOI：

  10.3987/com-14-12988
• 作为产物：
  描述：

  1-tert-butyl 3-methyl (3S,5R)-5-(2,2-dimethylbut-3-enoyl)piperidine-1,3-dicarboxylate 在 18-冠醚-6 、 lithium hydroxide monohydrate 、 O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate 、 臭氧 、 溶剂黄146 、 N,N-二异丙基乙胺 作用下， 以 四氢呋喃 、 二氯甲烷 、 N,N-二甲基乙酰胺 、 N,N-二甲基甲酰胺 、 甲苯 为溶剂， 反应 26.0h， 生成 tert-butyl (3S,5S)-3-[3,3-dimethyl-1-(o-tolyl)-6-oxo-2H-pyridin-4-yl]-5-{[(1R)-1-(5-fluoro-2-pyridyl)-3-methylbutyl]carbamoyl}piperidine-1-carboxylate
  参考文献：
  名称：

  An Efficient Synthesis of (3S,5S)-5-[3,3-Dimethyl-1-(o-tolyl)-6-oxo-2H-pyridin-4-yl]piperidine-3-carboxamide as Potent Renin Inhibitor

  摘要：

  We report synthesis and biological evaluation of (3S,5S)-5-[3,3-dimethyl-1-(o-tolyl)-6-oxo-2H-pyridin-4-yl]piperidine-3-carboxamide as renin inhibitor. This effective synthetic route involves a zinc mediated Barbier reaction and an intramolecular Horner-Wadsworth-Emmons reaction of sterically hindered ketone as key reactions. The prepared compound 4 exhibited both potent renin inhibitory activity and significant in vivo efficacy in furosemide pretreated cynomolgus monkeys.

  DOI：

  10.3987/com-14-12988