4-(dimethylamino)-N-ethyl-6-methoxypyrimidine-2-carboxamide

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪类
• 英文名称: 4-(dimethylamino)-N-ethyl-6-methoxypyrimidine-2-carboxamide
• 化学式: C₁₀H₁₆N₄O₂
• 分子量: 224.263
• InChiKey: VWYGCDCVWPUYSD-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.9
• 重原子数：
  16
• 可旋转键数：
  4
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  67.4
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  (2,6-二氯-嘧啶-4-基)-二甲胺 在 (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride 、 lithium hydroxide monohydrate 、 水 、 sodium 、 三乙胺 、 N,N-二异丙基乙胺 、 N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate 作用下， 以 甲醇 、 N,N-二甲基甲酰胺 为溶剂， 20.0~100.0 ℃ 、1.5 MPa 条件下， 反应 50.0h， 生成 4-(dimethylamino)-N-ethyl-6-methoxypyrimidine-2-carboxamide
  参考文献：
  名称：

  Effect of water solvation on the lipophilicity of isomeric pyrimidine-carboxamides

  摘要：

  Incorporation of nitrogen is a common medicinal chemistry tactic to reduce log D values. Neighboring group participation influences log D, so the results are isomer dependent. The log D and log P differences observed between isomeric pyrimidines 1, 2 and 3 presumably result when the carbonyl or ether lone pairs are in close proximity to a heterocyclic nitrogen lone pair, recruiting water to bridge between the electron rich atoms. Various lipophilicity calculators did not discriminate between 1 (log D = 2.6) and 3 (log D = 1.0), but solvation energies using Poisson-Boltzmann and 3D-RISM methods rationalize the observed differences in lipophilicity among pyrimidine carboxamide isomers. (C) 2015 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2015.04.041

文献信息

• Effect of water solvation on the lipophilicity of isomeric pyrimidine-carboxamides
  作者：Maria Angelica Linton、Benjamin J. Burke、Ted W. Johnson、Sacha Ninkovic、Ketan S. Gajiwala、Paul Richardson、Phuong T. Le

  DOI：10.1016/j.bmc.2015.04.041

  日期：2015.7

  Incorporation of nitrogen is a common medicinal chemistry tactic to reduce log D values. Neighboring group participation influences log D, so the results are isomer dependent. The log D and log P differences observed between isomeric pyrimidines 1, 2 and 3 presumably result when the carbonyl or ether lone pairs are in close proximity to a heterocyclic nitrogen lone pair, recruiting water to bridge between the electron rich atoms. Various lipophilicity calculators did not discriminate between 1 (log D = 2.6) and 3 (log D = 1.0), but solvation energies using Poisson-Boltzmann and 3D-RISM methods rationalize the observed differences in lipophilicity among pyrimidine carboxamide isomers. (C) 2015 Elsevier Ltd. All rights reserved.