3-bromo-6,7-dihydro-5H-pyrrolo[2,1-c][1,2,4]triazole | 1540389-59-0

• 分子结构分类: 有机化合物 - 有机卤素化合物 - 芳基卤化物
• 英文名称: 3-bromo-6,7-dihydro-5H-pyrrolo[2,1-c][1,2,4]triazole
• 英文别名: 3-Bromo-5H,6H,7H-pyrrolo[2,1-c][1,2,4]triazole
• CAS: 1540389-59-0
• 化学式: C₅H₆BrN₃
• 分子量: 188.027
• InChiKey: BTPCIRMLTUIDND-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.8
• 重原子数：
  9
• 可旋转键数：
  0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.6
• 拓扑面积：
  30.7
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  3-bromo-6,7-dihydro-5H-pyrrolo[2,1-c][1,2,4]triazole 在 四(三苯基膦)钯 、 sodium carbonate 作用下， 以 1,4-二氧六环 为溶剂， 反应 3.5h， 生成 N-(4-(6,7-dihydro-5H-pyrrolo[2,1-c][1,2,4]triazol-3-yl)-2-methoxyphenyl)formamide
  参考文献：
  名称：

  Introduction of a Methyl Group Curbs Metabolism of Pyrido[3,4-d]pyrimidine Monopolar Spindle 1 (MPS1) Inhibitors and Enables the Discovery of the Phase 1 Clinical Candidate N²-(2-Ethoxy-4-(4-methyl-4H-1,2,4-triazol-3-yl)phenyl)-6-methyl-N⁸-neopentylpyrido[3,4-d]pyrimidine-2,8-diamine (BOS172722)

  摘要：

  Monopolar spindle 1 (MPS1) occupies a central role in mitosis and is one of the main components of the spindle assembly checkpoint. The MPS1 kinase is an attractive cancer target, and herein, we report the discovery of the clinical candidate BOS172722. The starting point for our work was a series of pyrido[3,4-d]pyrimidine inhibitors that demonstrated excellent potency and kinase selectivity but suffered from rapid turnover in human liver microsomes (HLM). Optimizing HLM stability proved challenging since it was not possible to identify a consistent site of metabolism and lowering lipophilicity proved unsuccessful. Key to overcoming this problem was the finding that introduction of a methyl group at the 6-position of the pyrido[3,4-d]pyrimidine core significantly improved HLM stability. Met ID studies suggested that the methyl group suppressed metabolism at the distant aniline portion of the molecule, likely by blocking the preferred pharmacophore through which P450 recognized the compound. This work ultimately led to the discovery of BOS172722 as a Phase 1 clinical candidate.

  DOI：

  10.1021/acs.jmedchem.8b00690
• 作为产物：
  描述：

  6,7-dihydro-5H-pyrrolo[2,1-c][1,2,4]triazole hydrochloride 在 potassium carbonate 、 溴 、 sodium carbonate 作用下， 以 二氯甲烷 为溶剂， 以84.3 %的产率得到3-bromo-6,7-dihydro-5H-pyrrolo[2,1-c][1,2,4]triazole
  参考文献：
  名称：

  环状亚胺酸酯与 2-肼基-2-氧代乙酸甲酯反应的脂环环化三唑与三嗪二酮

  摘要：

  提出了一种合成环化三唑-3-羧酸和/或1,2,4-三嗪-5,6-二酮衍生物的酯的简单方便的方法。根据反应条件，用 2-肼基-2-氧代乙酸甲酯加热环状亚胺酯得到环化三唑或环化三嗪二酮。在盐酸加热下，1,2,4-三嗪-5,6-二酮转化为三唑。

  DOI：

  10.3987/com-21-14612