1-ethyl-N-(2-fluoro-5-hydroxyphenyl)-3-methyl-1H-pyrazole-4-carboxamide | 1451192-49-6

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 1-ethyl-N-(2-fluoro-5-hydroxyphenyl)-3-methyl-1H-pyrazole-4-carboxamide
• 英文别名: 1-ethyl-N-(2-fluoro-5-hydroxyphenyl)-3-methylpyrazole-4-carboxamide
• CAS: 1451192-49-6
• 化学式: C₁₃H₁₄FN₃O₂
• 分子量: 263.271
• InChiKey: HABZROXAQFGMTH-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.5
• 重原子数：
  19
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.23
• 拓扑面积：
  67.2
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  N-(6-chloroimidazo[1,2-b]pyridazin-2-yl)cyclopropanecarboxamide 、 1-ethyl-N-(2-fluoro-5-hydroxyphenyl)-3-methyl-1H-pyrazole-4-carboxamide 在 caesium carbonate 作用下， 以 二甲基亚砜 为溶剂， 反应 4.0h， 以85%的产率得到N-(5-{[2-(cyclopropanecarboxamido)imidazo[1,2-b]pyridazin-6-yl]oxy}-2-fluorophenyl)-1-ethyl-3-methyl-1H-pyrazole-4-carboxamide
  参考文献：
  名称：

  Convergent and streamlined synthesis of 6-etherified imidazo[1,2-b]pyridazine-2-amine derivatives possessing VEGFR-2 kinase inhibitory activity

  摘要：

  A convergent and streamlined synthesis of selective vascular endothelial growth factor receptor (VEGFR) 2 kinase inhibitors has been achieved using a synthetic strategy based on an SNAr reaction of 6-chloroimidazo[1,2-b]pyridazine with phenols in the final step. For the synthesis of 6-chloroimidazo[1,2-b]pyridazine, a one-pot reaction using 3-amino-6-chloropyridazine, cyclopropanecarboxamide, and bromoacetyl bromide was developed. The phenols were easily prepared by chemoselective acylation of 3-aminophenols with pyrazole carboxylic acids, and an efficient and high-yielding synthesis of N-ethylpyrazole was also developed. The SNAr reaction of 6-chloroimidazo[1,2-b]pyridazine with phenols in DMSO in the presence of cesium carbonate successfully proceeded at 100-110 degrees C to give the target products in good yields. This new chromatography-free process will be not only useful for the further bulk supply of these compounds but also applicable to the synthesis of other compounds containing the 6-etherified imidazo[1,2-b]pyridazin-2-amine core. (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.tet.2013.07.087
• 作为产物：
  描述：

  2-乙氧亚甲基乙酰乙酸乙酯 在 氯化亚砜 作用下， 以 乙二醇二甲醚 、 N,N-二甲基乙酰胺 为溶剂， 反应 4.0h， 生成 1-ethyl-N-(2-fluoro-5-hydroxyphenyl)-3-methyl-1H-pyrazole-4-carboxamide
  参考文献：
  名称：

  Convergent and streamlined synthesis of 6-etherified imidazo[1,2-b]pyridazine-2-amine derivatives possessing VEGFR-2 kinase inhibitory activity

  摘要：

  A convergent and streamlined synthesis of selective vascular endothelial growth factor receptor (VEGFR) 2 kinase inhibitors has been achieved using a synthetic strategy based on an SNAr reaction of 6-chloroimidazo[1,2-b]pyridazine with phenols in the final step. For the synthesis of 6-chloroimidazo[1,2-b]pyridazine, a one-pot reaction using 3-amino-6-chloropyridazine, cyclopropanecarboxamide, and bromoacetyl bromide was developed. The phenols were easily prepared by chemoselective acylation of 3-aminophenols with pyrazole carboxylic acids, and an efficient and high-yielding synthesis of N-ethylpyrazole was also developed. The SNAr reaction of 6-chloroimidazo[1,2-b]pyridazine with phenols in DMSO in the presence of cesium carbonate successfully proceeded at 100-110 degrees C to give the target products in good yields. This new chromatography-free process will be not only useful for the further bulk supply of these compounds but also applicable to the synthesis of other compounds containing the 6-etherified imidazo[1,2-b]pyridazin-2-amine core. (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.tet.2013.07.087

文献信息

• Convergent and streamlined synthesis of 6-etherified imidazo[1,2-b]pyridazine-2-amine derivatives possessing VEGFR-2 kinase inhibitory activity
  作者：Kazuhisa Ishimoto、Yasuhiro Sawai、Naohiro Fukuda、Toshiaki Nagata、Tomomi Ikemoto

  DOI：10.1016/j.tet.2013.07.087

  日期：2013.10

  A convergent and streamlined synthesis of selective vascular endothelial growth factor receptor (VEGFR) 2 kinase inhibitors has been achieved using a synthetic strategy based on an SNAr reaction of 6-chloroimidazo[1,2-b]pyridazine with phenols in the final step. For the synthesis of 6-chloroimidazo[1,2-b]pyridazine, a one-pot reaction using 3-amino-6-chloropyridazine, cyclopropanecarboxamide, and bromoacetyl bromide was developed. The phenols were easily prepared by chemoselective acylation of 3-aminophenols with pyrazole carboxylic acids, and an efficient and high-yielding synthesis of N-ethylpyrazole was also developed. The SNAr reaction of 6-chloroimidazo[1,2-b]pyridazine with phenols in DMSO in the presence of cesium carbonate successfully proceeded at 100-110 degrees C to give the target products in good yields. This new chromatography-free process will be not only useful for the further bulk supply of these compounds but also applicable to the synthesis of other compounds containing the 6-etherified imidazo[1,2-b]pyridazin-2-amine core. (C) 2013 Elsevier Ltd. All rights reserved.