ethyl 8-fluoro-7-(3-methoxyphenyl)-4-oxo-1H-pyrrolo[1,2-a]pyrimidine-3-carboxylate | 519156-85-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯
• 英文名称: ethyl 8-fluoro-7-(3-methoxyphenyl)-4-oxo-1H-pyrrolo[1,2-a]pyrimidine-3-carboxylate
• CAS: 519156-85-5
• 化学式: C₁₇H₁₅FN₂O₄
• 分子量: 330.316
• InChiKey: LIZKUKBDEJTSFJ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.9
• 重原子数：
  24
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.18
• 拓扑面积：
  69.6
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  ethyl 8-fluoro-7-(3-methoxyphenyl)-4-oxo-1H-pyrrolo[1,2-a]pyrimidine-3-carboxylate 在 四丁基氟化铵 、 溶剂黄146 作用下， 以 四氢呋喃 、 乙二醇二甲醚 为溶剂， 反应 17.5h， 生成 8-Fluoro-1-(2-fluoro-benzyl)-7-(3-methoxy-phenyl)-6-{[methyl-(2-pyridin-2-yl-ethyl)-amino]-methyl}-4-oxo-1,4-dihydro-pyrrolo[1,2-a]pyrimidine-3-carboxylic acid ethyl ester
  参考文献：
  名称：

  A novel synthesis of 7-aryl-8-fluoro-pyrrolo[1,2-a]pyrimid-4-ones as potent, stable GnRH receptor antagonists

  摘要：

  A new class of small molecule GnRH antagonists, the 7-aryl-8-fluoro-pyrrolo[1,2-a]pyrimid-4-ones, was designed and a novel synthesis for these compounds was developed. The synthesis utilizes a base-catalyzed intramolecular cyclization of fluoromethyl pyrimidone 5 to generate the bicyclic core. Amongst the compounds synthesized, we discovered some highly potent GnRH receptor antagonists (e.g., 12. K-i = 9 nM), which showed enhanced stability towards acidic physiological conditions compared to the des-fluoro analogues. (C) 2002 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0960-894x(02)00745-x
• 作为产物：
  描述：

  ethyl 2-(fluoromethyl)-6-oxo-1H-pyrimidine-5-carboxylate 在 四丁基氟化铵 、 sodium ethanolate 作用下， 以 四氢呋喃 、 乙二醇二甲醚 、 乙醇 为溶剂， 反应 4.5h， 生成 ethyl 8-fluoro-7-(3-methoxyphenyl)-4-oxo-1H-pyrrolo[1,2-a]pyrimidine-3-carboxylate
  参考文献：
  名称：

  A novel synthesis of 7-aryl-8-fluoro-pyrrolo[1,2-a]pyrimid-4-ones as potent, stable GnRH receptor antagonists

  摘要：

  A new class of small molecule GnRH antagonists, the 7-aryl-8-fluoro-pyrrolo[1,2-a]pyrimid-4-ones, was designed and a novel synthesis for these compounds was developed. The synthesis utilizes a base-catalyzed intramolecular cyclization of fluoromethyl pyrimidone 5 to generate the bicyclic core. Amongst the compounds synthesized, we discovered some highly potent GnRH receptor antagonists (e.g., 12. K-i = 9 nM), which showed enhanced stability towards acidic physiological conditions compared to the des-fluoro analogues. (C) 2002 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0960-894x(02)00745-x