(2S)-N-(6-bromopyridin-3-yl)-1-[4-[(5-cyclopropyl-1H-pyrazol-3-yl)amino]pyrrolo[2,1-f][1,2,4]triazin-2-yl]-2-methylpyrrolidine-2-carboxamide | 1446701-46-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯并三嗪类
• 英文名称: (2S)-N-(6-bromopyridin-3-yl)-1-[4-[(5-cyclopropyl-1H-pyrazol-3-yl)amino]pyrrolo[2,1-f][1,2,4]triazin-2-yl]-2-methylpyrrolidine-2-carboxamide
• CAS: 1446701-46-7
• 化学式: C₂₃H₂₄BrN₉O
• 分子量: 522.407
• InChiKey: PJJHJFAJJLREAB-QHCPKHFHSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  34
• 可旋转键数：
  6
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.35
• 拓扑面积：
  116
• 氢给体数：
  3
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  (2S)-N-(6-bromopyridin-3-yl)-1-[4-[(5-cyclopropyl-1H-pyrazol-3-yl)amino]pyrrolo[2,1-f][1,2,4]triazin-2-yl]-2-methylpyrrolidine-2-carboxamide 在 [18F]-tetrabutylammonium fluoride 作用下， 以 二甲基亚砜 为溶剂， 反应 0.5h， 以8%的产率得到[18F](S)-1-(4-((5-cyclopropyl-1H-pyrazol-3-yl)amino)pyrrolo[2,1-f][1,2,4]triazin-2-yl)-N-(6-fluoropyridin-3-yl)-2-methylpyrrolidine-2-carboxamide
  参考文献：
  名称：

  Synthesis and in vitro evaluation of [18F]BMS-754807: A potential PET ligand for IGF-1R

  摘要：

  Radiosynthesis and in vitro evaluation of [F-18](S)-1-(4-((5-cyclopropyl-1H-pyrazol-3-yl)amino)pyrrolo[ 2,1-f][1,2,4]triazin-2-yl)-N-(6-fluoropyridin-3-yl)-2-methylpyrrolidine-2-carboxamide ([F-18]BMS-754807 or [F-18]1) a specific IGF-1R inhibitor was performed. [F-18]1 demonstrated specific binding in vitro to human cancer tissues. Synthesis of reference standard 1 and corresponding bromo derivative (1a), the precursor for radiolabeling were achieved from 2,4-dichloropyrrolo[2,1-f][1,2,4] triazine (4) in three steps with 50% overall yield. The radioproduct was obtained in 8% yield by reacting 1a with [F-18]TBAF in DMSO at 170 degrees C at high radiochemical purity and specific activity (1-2 Ci/mu mol, N = 10). The proof of concept of IGF-IR imaging with [F-18]1 was demonstrated by in vitro autoradiography studies using pathologically identified surgically removed grade IV glioblastoma, breast cancer and pancreatic tumor tissues. These studies indicate that [F-18]1 can be a potential PET tracer for monitoring IGF-1R. (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2013.05.026
• 作为产物：
  描述：

  2,4-二氯吡咯并[2,1-f][1,2,4]三嗪 在 氯化亚砜 、 potassium tert-butylate 、 N,N-二异丙基乙胺 作用下， 以 N-甲基吡咯烷酮 、 N,N-二甲基甲酰胺 、 异丙醇 为溶剂， 反应 25.0h， 生成 (2S)-N-(6-bromopyridin-3-yl)-1-[4-[(5-cyclopropyl-1H-pyrazol-3-yl)amino]pyrrolo[2,1-f][1,2,4]triazin-2-yl]-2-methylpyrrolidine-2-carboxamide
  参考文献：
  名称：

  Synthesis and in vitro evaluation of [18F]BMS-754807: A potential PET ligand for IGF-1R

  摘要：

  Radiosynthesis and in vitro evaluation of [F-18](S)-1-(4-((5-cyclopropyl-1H-pyrazol-3-yl)amino)pyrrolo[ 2,1-f][1,2,4]triazin-2-yl)-N-(6-fluoropyridin-3-yl)-2-methylpyrrolidine-2-carboxamide ([F-18]BMS-754807 or [F-18]1) a specific IGF-1R inhibitor was performed. [F-18]1 demonstrated specific binding in vitro to human cancer tissues. Synthesis of reference standard 1 and corresponding bromo derivative (1a), the precursor for radiolabeling were achieved from 2,4-dichloropyrrolo[2,1-f][1,2,4] triazine (4) in three steps with 50% overall yield. The radioproduct was obtained in 8% yield by reacting 1a with [F-18]TBAF in DMSO at 170 degrees C at high radiochemical purity and specific activity (1-2 Ci/mu mol, N = 10). The proof of concept of IGF-IR imaging with [F-18]1 was demonstrated by in vitro autoradiography studies using pathologically identified surgically removed grade IV glioblastoma, breast cancer and pancreatic tumor tissues. These studies indicate that [F-18]1 can be a potential PET tracer for monitoring IGF-1R. (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2013.05.026