Ethyl 2-(fluoromethyl)-1-[2-(3-methoxyphenyl)-2-oxoethyl]-6-oxopyrimidine-5-carboxylate | 519156-84-4

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: Ethyl 2-(fluoromethyl)-1-[2-(3-methoxyphenyl)-2-oxoethyl]-6-oxopyrimidine-5-carboxylate
• 英文别名: ethyl 2-(fluoromethyl)-1-[2-(3-methoxyphenyl)-2-oxoethyl]-6-oxopyrimidine-5-carboxylate
• CAS: 519156-84-4
• 化学式: C₁₇H₁₇FN₂O₅
• 分子量: 348.331
• InChiKey: XCLPQGULXAUDCI-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.6
• 重原子数：
  25
• 可旋转键数：
  8
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  85.3
• 氢给体数：
  0
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  Ethyl 2-(fluoromethyl)-1-[2-(3-methoxyphenyl)-2-oxoethyl]-6-oxopyrimidine-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 20.5h， 生成 8-Fluoro-1-(2-fluoro-benzyl)-7-(3-methoxy-phenyl)-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：

  2-溴-3‘-甲氧基苯乙酮 、 ethyl 2-(fluoromethyl)-6-oxo-1H-pyrimidine-5-carboxylate 在 四丁基氟化铵 作用下， 以 四氢呋喃 、 乙二醇二甲醚 为溶剂， 反应 0.5h， 生成 2-Fluoromethyl-4-[2-(3-methoxy-phenyl)-2-oxo-ethoxy]-pyrimidine-5-carboxylic acid ethyl ester 、 Ethyl 2-(fluoromethyl)-1-[2-(3-methoxyphenyl)-2-oxoethyl]-6-oxopyrimidine-5-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

文献信息

• A novel synthesis of 7-aryl-8-fluoro-pyrrolo[1,2-a]pyrimid-4-ones as potent, stable GnRH receptor antagonists
  作者：Fabio C. Tucci、Yun-Fei Zhu、Zhiqiang Guo、Timothy D. Gross、Patrick J. Connors、R.Scott Struthers、Greg J. Reinhart、Xiaochuan Wang、John Saunders、Chen Chen

  DOI：10.1016/s0960-894x(02)00745-x

  日期：2002.12

  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.