(E)-1-chloro-4-morpholino-2-butene | 4633-96-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 恶嗪烷类
• 英文名称: (E)-1-chloro-4-morpholino-2-butene
• 英文别名: 4-(4-chloro-but-2-enyl)-morpholine；1-Morpholino-4-chlor-trans-buten；4-[(E)-4-chlorobut-2-enyl]morpholine
• CAS: 4633-96-9
• 化学式: C₈H₁₄ClNO
• 分子量: 175.658
• InChiKey: RBMOHURSRGLBOW-OWOJBTEDSA-N

物化性质

• 沸点：
  86-87 °C(Press: 0.7 Torr)
• 密度：
  1.070±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.8
• 重原子数：
  11
• 可旋转键数：
  3
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.75
• 拓扑面积：
  12.5
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  6-甲基-2-苯基嘧啶-4-酮 、 (E)-1-chloro-4-morpholino-2-butene 在 potassium carbonate 、 potassium iodide 作用下， 以 乙腈 为溶剂， 生成 (E)-4-(4-((6-methyl-2-phenylpyrimidin-4-yl)oxy)but-2-en-1-yl)morpholine
  参考文献：
  名称：

  Synthesis and Biological Evaluation of Novel Sigma-1 Receptor Antagonists Based on Pyrimidine Scaffold As Agents for Treating Neuropathic Pain

  摘要：

  The discovery and synthesis of a new series of pyrimidines as potent sigma-1 receptor (sigma R-1) antagonists, associated with pharmacological antineuropathic pain activity, are the focus of this article. The new compounds were evaluated in vitro in sigma-1 and sigma-2 receptor binding assays. The nature of the pyrimidine scaffold was crucial for activity, and a basic amine was shown to be necessary according to the known pharmacophoric model. The most promising derivative was 5-chloro-2-(4-chlorophenyl)-4-methyl-6-(3-(piperidin-1-yl)propoxy)pyrimidine (137), which exhibited a high binding affinity to sigma R-1 receptor (K-i sigma(1) = 1.06 nM) and good sigma-1/2 selectivity (1344-fold). In in vivo tests, compound 137 exerted dose-dependent antinociceptive effects in mice formalin model and rats CCI models of neuropathic pain. In addition, no motor impairments were found in rotarod tests; acceptable pharmacokinetic properties were also noted. These data suggest compound 137 may constitute a novel class of drugs for the treatment of neuropathic pain.

  DOI：

  10.1021/jm501207r
• 作为产物：
  描述：

  吗啉 、 反式-1,4-二氯-2-丁烯 以 四氢呋喃 为溶剂， 反应 5.0h， 以54%的产率得到(E)-1-chloro-4-morpholino-2-butene
  参考文献：
  名称：

  DTBB催化的4-官能化1-氯-2-丁烯的锂化反应

  摘要：

  的反应Ñ，Ñ二取代（ê）-4-氨基-1-氯-2-丁烯1与过量锂和DTBB的亲电子[E的存在催化量+ =卜吨CHO，苯甲醛，在-78°C下于THF中的Me 2 CO，（CH 2）5 CO，（c -C 3 H 5）2 CO，Me 3 SiCl]在水中水解后，得到预期的1,2-混合物和1,4-二取代的化合物（2和3，分别），可通过快速色谱法轻松分离。当将反应应用于相应的（Z）-起始原料或应用于（Z）-或（E）-氧或含硫的氯化2-丁烯时，其收率要低于硝化前体的收率。

  DOI：

  10.1016/0040-4020(96)00798-3

文献信息

• Synthesis and Biological Evaluation of Novel Sigma-1 Receptor Antagonists Based on Pyrimidine Scaffold As Agents for Treating Neuropathic Pain
  作者：Yu Lan、Yin Chen、Xudong Cao、Juecheng Zhang、Jie Wang、Xiangqing Xu、Yinli Qiu、Tan Zhang、Xin Liu、Bi-Feng Liu、Guisen Zhang

  DOI：10.1021/jm501207r

  日期：2014.12.26

  The discovery and synthesis of a new series of pyrimidines as potent sigma-1 receptor (sigma R-1) antagonists, associated with pharmacological antineuropathic pain activity, are the focus of this article. The new compounds were evaluated in vitro in sigma-1 and sigma-2 receptor binding assays. The nature of the pyrimidine scaffold was crucial for activity, and a basic amine was shown to be necessary according to the known pharmacophoric model. The most promising derivative was 5-chloro-2-(4-chlorophenyl)-4-methyl-6-(3-(piperidin-1-yl)propoxy)pyrimidine (137), which exhibited a high binding affinity to sigma R-1 receptor (K-i sigma(1) = 1.06 nM) and good sigma-1/2 selectivity (1344-fold). In in vivo tests, compound 137 exerted dose-dependent antinociceptive effects in mice formalin model and rats CCI models of neuropathic pain. In addition, no motor impairments were found in rotarod tests; acceptable pharmacokinetic properties were also noted. These data suggest compound 137 may constitute a novel class of drugs for the treatment of neuropathic pain.
• DTBB-catalysed lithiation of 4-functionalised 1-chloro-2-butenes
  作者：Fernando F Huerta、Cecilia Gómez、Miguel Yus

  DOI：10.1016/0040-4020(96)00798-3

  日期：1996.10

  The reaction of N,N-disubstituted (E)-4-amino-1-chloro-2-butenes 1 with an excess of lithium and a catalytic amount of DTBB in the presence of an electrophile [E+ = ButCHO, PhCHO, Me2CO, (CH2)5CO, (c-C3H5)2CO, Me3SiCl] in THF at −78°C leads, after hydrolysis with water, to the expected mixture of 1,2- and 1,4- disubstituted compounds (2 and 3, respectively), which could be easily separated by flash

  的反应Ñ，Ñ二取代（ê）-4-氨基-1-氯-2-丁烯1与过量锂和DTBB的亲电子[E的存在催化量+ =卜吨CHO，苯甲醛，在-78°C下于THF中的Me 2 CO，（CH 2）5 CO，（c -C 3 H 5）2 CO，Me 3 SiCl]在水中水解后，得到预期的1,2-混合物和1,4-二取代的化合物（2和3，分别），可通过快速色谱法轻松分离。当将反应应用于相应的（Z）-起始原料或应用于（Z）-或（E）-氧或含硫的氯化2-丁烯时，其收率要低于硝化前体的收率。