4,6-dichloro-1-methyl-2-oxa-5-azabicyclo<2.2.2>oct-5-en-3-one | 125849-97-0

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: 4,6-dichloro-1-methyl-2-oxa-5-azabicyclo<2.2.2>oct-5-en-3-one
• 英文别名: 4,6-Dichloro-1-methyl-2-oxa-5-azabicyclo[2.2.2]oct-5-en-3-one
• CAS: 125849-97-0
• 化学式: C₇H₇Cl₂NO₂
• 分子量: 208.044
• InChiKey: NAJHAIWITZCCBN-UHFFFAOYSA-N

物化性质

• 沸点：
  343.2±52.0 °C(Predicted)
• 密度：
  1.66±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.8
• 重原子数：
  12
• 可旋转键数：
  0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.71
• 拓扑面积：
  38.7
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  4,6-dichloro-1-methyl-2-oxa-5-azabicyclo<2.2.2>oct-5-en-3-one 在 palladium on activated charcoal 氢气 、 碳酸氢钠 作用下， 以 乙醇 、 氯仿 为溶剂， 25.0 ℃ 、101.33 kPa 条件下， 反应 4.25h， 生成 (+/-)-ethyl 6-oxo-5-methyl-2-pyridinecarboxylate
  参考文献：
  名称：

  4,6-Dichloro-2-oxa-5-azabicyclo[2.2.2]oct-5-en-3-ones and their Use in the Synthesis of 1,6-Dihydro-6-oxo-2-pyridine- and 6-Oxo-2-piperidinecarboxylates

  摘要：

  4,6-Dichloro-2-oxa-5-azabicyclo[2.2.2]oct-5-en-3-ones obtained from cycloaddition of 2H-1,4-oxazin-2-ones and alkene compounds, undergo lactone cleavage with alcohols to yield 1,4,5,6-tetrahydro-5-hydroxy-6-oxo-2-pyridnecarboxylates which can be dehydrated or reduced to a afford 1,6-dihydro-6-oxo-2-pyridine- or 6-oxo-2-pipcridinecarboxylates.

  DOI：

  10.1016/0040-4020(95)01084-x
• 作为产物：
  描述：

  乙烯 、 3,5-二氯-6-甲基-1,4-噁唑-2-酮 以 甲苯 为溶剂， 110.0 ℃ 、2.03 MPa 条件下， 反应 0.5h， 以97%的产率得到4,6-dichloro-1-methyl-2-oxa-5-azabicyclo<2.2.2>oct-5-en-3-one
  参考文献：
  名称：

  Cycloaddition of Olefinic Compounds to 2H-1,4-Oxazin-2-ones: Synthesis of 2-Oxa-5-azabicyclo[2.2.2]oct-5-en-3-ones

  摘要：

  研究了 2H-1,4-恶嗪-2-酮 5 与烯烃的 [4 + 2] 环加成反应，以及生成新的 2-oxa-5-azabicyclo [2.2.2]oct-5-en-3-ones 类型 6 的过程。环化反应受噁嗪酮中 5-Cl 取代基的促进，可与贫电子和富电子烯烃进行。分离化合物的核磁共振数据显示，对称二取代的烯烃只形成内向加合物；这可以从次级轨道相互作用和内酯功能与外向过渡态的两个取代基之间的排斥力来解释。 在某些单取代烯烃中观察到的较低内向选择性与这种排斥因子的预期下降相一致。电子贫乏的丙烯酸甲酯的加成显示出相当低的区域选择性，但其他亲二烯化合物的加成总是具有很高的区域选择性，正交异构体更受青睐。

  DOI：

  10.1055/s-1992-26205

文献信息

• [EN] POSITIVE ALLOSTERIC MODULATORS OF MGLUR2<br/>[FR] MODULATEURS ALLOSTÉRIQUES POSITIFS DE MGLUR2
  申请人：MERCK SHARP & DOHME

  公开号：WO2011109277A1

  公开（公告）日：2011-09-09

  The present invention is directed to 5-substituted 1,3-dihydro-2,1,3-benzothiadiazole 2,2-dioxide and 1,3-dihydro[1,2,5]thiadiazolo[3,4-b]pyridine 2,2,-dioxide derivatives which are potentiators of metabotropic glutamate receptors, particularly the mGluR2 receptor, and which are useful in the treatment or prevention of neurological and psychiatric disorders associated with glutamate dysfunction and diseases in which metabotropic glutamate receptors are involved. The invention is also directed to pharmaceutical compositions comprising these compounds and the use of these compounds and compositions in the prevention or treatment of such diseases in which metabotropic glutamate receptors are involved.

  本发明涉及5-取代的1,3-二氢-2,1,3-苯并噻二唑-2,2-二氧化物和1,3-二氢[1,2,5]噻二唑并[3,4-b]吡啶-2,2-二氧化物衍生物，它们是代谢型谷氨酸受体的增强剂，特别是mGluR2受体，并且在治疗或预防与谷氨酸功能障碍相关的神经和精神疾病以及代谢型谷氨酸受体参与的疾病中非常有用。该发明还涉及含有这些化合物的药物组合物以及这些化合物和组合物在预防或治疗涉及代谢型谷氨酸受体的疾病中的用途。
• Generation of polysubstituted 2-pyridinecarboxylic acid derivatives from the reaction of (functionalised) 2-oxa-5-azabicyclo[2.2.2]oct-5-en-3-ones with various nucleophiles
  作者：Kristof J. Dubois、Christine C. Fannes、Suzanne M. Toppet、Georges J. Hoornaert

  DOI：10.1016/0040-4020(96)00733-8

  日期：1996.9

  By selective reaction of the chlorimine function in the adducts 2 from 3,5-dichloro-2H-1,4-oxazin-2-ones and double bond systems, a series of 6-substituted 2-oxa-5-azabicyclo[2.2.2]oct-5-en-3-ones 3 could be generated. Lactone cleavage of the latter with alcohols or amines yielded variously substituted 4,5-dihydro-5-hydroxy-2-pyridinecarboxylic acid derivatives which were dehydrated to afford the corresponding

  通过3,5-二氯-2 H -1,4-恶嗪-2-酮和双键体系中加合物2中氯亚胺官能团的选择性反应，形成一系列6-取代的2-恶唑-5-氮杂双环[2.2] .2]可以生成oct-5-en-3-ones 3。用醇或胺将后者的内酯裂解，得到各种取代的4，5-二氢-5-羟基-2-吡啶羧酸衍生物，将其脱水以得到相应的吡啶体系。通过使2与Me 3 Al /胺反应，可在一步步骤中获得一些6-氨基取代的2-吡啶甲酰胺。
• A new pathway to substituted 6-chloro-2-pyridinecarboxylic acid derivatives from the reaction of 4,6-dichloro-2-oxa-5-aza-bicyclo[2.2.2]oct-5-en-3-ones with nucleophiles
  作者：Kristof J. Dubois、Georges J. Hoornaert

  DOI：10.1016/0040-4020(96)00304-3

  日期：1996.5

  Reaction of alcohols or amines with 4,6-dichloro-2-oxa-5-azabicyclo[2.2.2]oct-5-en-3-ones gives direct conversion into (3,(4,))5-substituted 6-chloro-2-pyridinecarboxylic acid derivatives via selective lactone cleavage followed by rapid elimination of HCl and H2O in the presence of DBU.

  醇或胺与4,6-二氯-2-氧杂-5-氮杂双环[2.2.2] oct-5-en-3-ones的反应直接转化为（3，（4，））5-取代的6-通过选择性裂解内酯氯-2-吡啶羧酸衍生物，接着的盐酸和H迅速消除2在DBU存在O操作。
• POSITIVE ALLOSTERIC MODULATORS OF MGLUR2
  申请人：Layton Mark E.

  公开号：US20130158002A1

  公开（公告）日：2013-06-20

  The present invention is directed to 5-substituted 1,3-dihydro-2,1,3-benzothiadiazole 2,2-dioxide and 1,3-dihydro[1,2,5]thiadiazolo[3,4-b]pyridine 2,2,-dioxide derivatives which are potentiators of metabotropic glutamate receptors, particularly the mGluR2 receptor, and which are useful in the treatment or prevention of neurological and psychiatric disorders associated with glutamate dysfunction and diseases in which metabotropic glutamate receptors are involved. The invention is also directed to pharmaceutical compositions comprising these compounds and the use of these compounds and compositions in the prevention or treatment of such diseases in which metabotropic glutamate receptors are involved.

  本发明涉及5-取代的1,3-二氢-2,1,3-苯并噻二唑2,2-二氧化物和1,3-二氢[1,2,5]噻二唑并[3,4-b]吡啶2,2-二氧化物衍生物，它们是代谢型谷氨酸受体的增强剂，特别是mGluR2受体，并且可用于治疗或预防与谷氨酸功能障碍相关的神经和精神障碍以及代谢型谷氨酸受体参与的疾病。本发明还涉及包含这些化合物的药物组合物以及在预防或治疗代谢型谷氨酸受体参与的疾病中使用这些化合物和组合物。
• Positive allosteric modulators of mGluR2
  申请人：Layton Mark E.

  公开号：US09108937B2

  公开（公告）日：2015-08-18

  The present invention is directed to 5-substituted 1,3-dihydro-2,1,3-benzothiadiazole 2,2-dioxide and 1,3-dihydro[1,2,5]thiadiazolo[3,4-b]pyridine 2,2,-dioxide derivatives which are potentiators of metabotropic glutamate receptors, particularly the mGluR2 receptor, and which are useful in the treatment or prevention of neurological and psychiatric disorders associated with glutamate dysfunction and diseases in which metabotropic glutamate receptors are involved. The invention is also directed to pharmaceutical compositions comprising these compounds and the use of these compounds and compositions in the prevention or treatment of such diseases in which metabotropic glutamate receptors are involved.

  本发明涉及5-取代的1,3-二氢-2,1,3-苯并噻二唑2,2-二氧化物和1,3-二氢[1,2,5]噻二唑并[3,4-b]吡啶2,2-二氧化物衍生物，它们是代谢型谷氨酸受体（尤其是mGluR2受体）的增强剂，可用于治疗或预防与谷氨酸功能障碍相关的神经和精神障碍以及代谢型谷氨酸受体参与的疾病。本发明还涉及包含这些化合物的制药组合物以及这些化合物和组合物在预防或治疗代谢型谷氨酸受体参与的疾病中的使用。