2-苯胺基嘧啶-5-羧酸甲酯 | 937796-09-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪类
• 中文名称: 2-苯胺基嘧啶-5-羧酸甲酯
• 英文名称: Methyl 2-anilinopyrimidine-5-carboxylate
• CAS: 937796-09-3
• 化学式: C₁₂H₁₁N₃O₂
• 分子量: 229.238
• InChiKey: CAKVYPYBXAVALF-UHFFFAOYSA-N

物化性质

• 沸点：
  400.8±37.0 °C(Predicted)
• 密度：
  1.274±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.9
• 重原子数：
  17
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.08
• 拓扑面积：
  64.1
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  2-苯胺基嘧啶-5-羧酸甲酯 在 水 、 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 、 lithium hydroxide 作用下， 以 四氢呋喃 、 甲醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 15.0h， 生成 N-(2-methyl-5-((4-((4-methylpiperazin-1-yl)methyl)-3-(trifluoromethyl)phenyl)carbamoyl)phenyl)-2-(phenylamino)pyrimidine-5-carboxamide
  参考文献：
  名称：

  Identification and Optimization of New Dual Inhibitors of B-Raf and Epidermal Growth Factor Receptor Kinases for Overcoming Resistance against Vemurafenib

  摘要：

  Epidermal growth factor receptor (EGFR) amplification has been demonstrated to be critical for the inherent and/or acquired resistance against current B-Raf(V600E) inhibitor therapy for melanoma and colorectal cancer patients. We describe the discovery and structure-activity relationship study of a series of 1H-pyrazolo[3,4-b]pyridine-5-carboxamide analogues as novel dual inhibitors of EGFR and B-Raf(V600E) mutant. One of the most promising compounds, 6a, potently inhibited both of the kinases with IC50 values of 8.0 and 51 nM, respectively. The compound also strongly suppressed the proliferation of a panel of intrinsic and acquired resistant melanoma and/or colorectal cancer cells harboring overexpressed EGFR with submicromolar IC50 values. Further mechanism investigation revealed that 6a could sustainably inhibit the activation of the MAPK path way in the resistant SK-MEL-28 PR30 melanoma cancer cells and WiDr colorectal cancer cells with EGFR amplification. Our results support the hypothesis that the EGFR/B-Raf(V600E) dual inhibition might be a tractable strategy to overcome the intrinsic and acquired resistance of melanoma and/or colorectal cancers against the current B-Raf(V600E) inhibitor therapy.

  DOI：

  10.1021/jm500007h
• 作为产物：
  描述：

  苯胺 、 2-氯嘧啶-5-羧酸甲酯 在 溶剂黄146 作用下， 以 1,4-二氧六环 为溶剂， 生成 2-苯胺基嘧啶-5-羧酸甲酯
  参考文献：
  名称：

  通过受保护苯胺的对位选择性烷基化制备 α-芳基乙腈骨架的新方法

  摘要：

  在此，我们报道了以2-溴-2-氰基丙酸乙酯为新型烷基化试剂的钌催化对位选择性烷基化反应，直接形成具有季碳中心的α-芳基乙腈骨架。各种受保护的苯胺都可以耐受，以中等至良好的收率产生相应的产物。

  DOI：

  10.1002/chem.202300905

文献信息

• Identification and Optimization of New Dual Inhibitors of B-Raf and Epidermal Growth Factor Receptor Kinases for Overcoming Resistance against Vemurafenib
  作者：Huimin Cheng、Yu Chang、Lianwen Zhang、Jinfeng Luo、Zhengchao Tu、Xiaoyun Lu、Qingwen Zhang、Jibu Lu、Xiaomei Ren、Ke Ding

  DOI：10.1021/jm500007h

  日期：2014.3.27

  Epidermal growth factor receptor (EGFR) amplification has been demonstrated to be critical for the inherent and/or acquired resistance against current B-Raf(V600E) inhibitor therapy for melanoma and colorectal cancer patients. We describe the discovery and structure-activity relationship study of a series of 1H-pyrazolo[3,4-b]pyridine-5-carboxamide analogues as novel dual inhibitors of EGFR and B-Raf(V600E) mutant. One of the most promising compounds, 6a, potently inhibited both of the kinases with IC50 values of 8.0 and 51 nM, respectively. The compound also strongly suppressed the proliferation of a panel of intrinsic and acquired resistant melanoma and/or colorectal cancer cells harboring overexpressed EGFR with submicromolar IC50 values. Further mechanism investigation revealed that 6a could sustainably inhibit the activation of the MAPK path way in the resistant SK-MEL-28 PR30 melanoma cancer cells and WiDr colorectal cancer cells with EGFR amplification. Our results support the hypothesis that the EGFR/B-Raf(V600E) dual inhibition might be a tractable strategy to overcome the intrinsic and acquired resistance of melanoma and/or colorectal cancers against the current B-Raf(V600E) inhibitor therapy.
• A Novel Approach to α‐Arylacetonitrile Skeletons via para‐Selective Alkylation of Protected Anilines
  作者：Zefeng Deng、Weitai Fan、Jian Liu、Guangliang Tu、Pengcheng Huang、Xu Xu、Jie Tan、Shun‐Jun Ji、Yingsheng Zhao

  DOI：10.1002/chem.202300905

  日期：2023.8.4

  Herein, we report a ruthenium-catalyzed para-selective alkylation reaction with ethyl 2-bromo-2-cyanopropanoate as the novel alkylating reagent to directly form an α-arylacetonitrile skeleton with quaternary carbon center. Various protected anilines were tolerated, yielding the corresponding products in moderate to good yields.

  在此，我们报道了以2-溴-2-氰基丙酸乙酯为新型烷基化试剂的钌催化对位选择性烷基化反应，直接形成具有季碳中心的α-芳基乙腈骨架。各种受保护的苯胺都可以耐受，以中等至良好的收率产生相应的产物。