6-溴-8-甲氧基咪唑并[1,2-A]吡嗪 | 63744-25-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 咪唑并吡嗪类
• 中文名称: 6-溴-8-甲氧基咪唑并[1,2-A]吡嗪
• 英文名称: 6-bromo-8-methoxyimidazo[1,2-a]pyrazine
• CAS: 63744-25-2
• 化学式: C₇H₆BrN₃O
• 分子量: 228.048
• InChiKey: NFZLMWYHNQPCDZ-UHFFFAOYSA-N

物化性质

• 密度：
  1.80±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2
• 重原子数：
  12
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.14
• 拓扑面积：
  39.4
• 氢给体数：
  0
• 氢受体数：
  3

安全信息

• 海关编码：
  2933990090
• 危险性防范说明：
  P280,P305+P351+P338
• 危险性描述：
  H302
• 储存条件：
  存储条件：2-8°C，密封保存，置于干燥处。

反应信息

• 作为反应物：
  描述：

  6-溴-8-甲氧基咪唑并[1,2-A]吡嗪 在 palladium on activated charcoal 氢气 作用下， 生成 8-甲氧基咪唑并[1,2-a]吡嗪
  参考文献：
  名称：

  Synthesis and antibronchospastic activity of 8-alkoxy- and 8-(alkylamino)imidazo[1,2-a]pyrazines

  摘要：

  Theophylline still occupies a dominant place in asthma therapy. Unfortunatly its adverse central nervous system (CNS) stimulant effects can dramatically limit its use, and adjustments in the dosage are often needed. We have synthesized a new series of imidazo[1,2-a]pyrazine derivatives which are much more potent bronchodilators than theophylline in vivo and do not exhibit the CNS stimulatory profile. In vitro studies on isolated rat uterus and guinea pig trachea confirm the high potentialities of these derivatives. 6-Bromo-8-(methylamino)imidazo[1,2-a]pyrazine-3-carbonitrile (23) is identified as the most potent compound of the series. As in the case of theophylline, phosphodiesterase inhibition appears unlikely to be the unique mechanism of action of this series of heterocycles.

  DOI：

  10.1021/jm00096a008
• 作为产物：
  描述：

  sodium methylate 、 6,8-二溴咪唑并[1,2-a]吡嗪 以 甲醇 为溶剂， 反应 1.0h， 生成 6-溴-8-甲氧基咪唑并[1,2-A]吡嗪
  参考文献：
  名称：

  [EN] UREA OREXIN RECEPTOR AGONISTS
  [FR] AGONISTES DU RÉCEPTEUR DE L'OREXINE D'URÉE

  摘要：

  本发明涉及尿素化合物，其为促进荷尔蒙受体的激动剂。本发明还涉及所述化合物在潜在治疗或预防神经系统和精神疾病中的应用，其中荷尔蒙受体参与其中。本发明还涉及包含这些化合物的组合物。本发明还涉及这些组合物在潜在预防或治疗荷尔蒙受体参与的疾病中的应用。

  公开号：

  WO2022132696A1

文献信息

• Palladium Catalyzed One-Pot Sequential Suzuki Cross-Coupling–Direct C–H Functionalization of Imidazo[1,2-<i>a</i>]pyrazines
  作者：Vincent Gembus、Jean-François Bonfanti、Olivier Querolle、Philippe Jubault、Vincent Levacher、Christophe Hoarau

  DOI：10.1021/ol3029059

  日期：2012.12.7

  functionalization at C3/C6 of imidazo[1,2-a]pyrazines has been developed via a palladium-catalyzed sequential Suzuki–Miyaura cross-coupling/direct C–H arylation, vinylation, and benzylation. The procedure remains effective in the presence of a methyl thioether group at C8, which may in turn be successfully engaged in a cross-coupling method to afford 3,6,8-trisubstituted imidazo[1,2-a]pyrazines. This work paves

  通过钯催化的连续Suzuki-Miyaura交叉偶联/直接C-H芳基化，乙烯基化和苄基化，已经开发出了咪唑并[1,2- a ]吡嗪在C3 / C6处有效的“一锅”选择性功能化。该过程在C 8处存在甲基硫醚基的情况下仍然有效，该甲基硫醚基可以依次成功地以交叉偶联方法得到3,6,8-三取代的咪唑并[1,2- a ]吡嗪。这项工作为咪唑并[1,2- a ]吡嗪系列生物相关化合物的设计铺平了道路。
• Aza-indolizine with bridgehead nitrogen. Metalation, halogen-metal exchange and directed ortho-lithiation in the imidazo[1,2-a]pyrazine series
  作者：Olivier Vitse、Jacques Bompart、Guy Subra、Henri Viols、Roger Escale、Jean P. Chapat、Pierre A. Bonnet

  DOI：10.1016/s0040-4020(98)00287-7

  日期：1998.6

  The n-BuLi and lithium 2,2,6,6-tetramethylpiperidine (LTMP) metalation of imidazo[1,2-a]pyrazine heterocycles and subsequent quenching with electrophiles is described. Bromine atoms exhibit different behaviours towards lithiation depending on their positions (3 or 6) on the imidazo[1,2-a]pyrazine heterocycle. Halogen-metal exchange occurs readily with the bromine on position 3. On the contrary, bromine

  描述了咪唑并[1,2- a ]吡嗪杂环的n -BuLi和2,2,6,6-四甲基哌啶锂（LTMP）金属化以及随后用亲电试剂的猝灭。溴原子根据其在咪唑并[1,2- a ]吡嗪杂环上的位置（3或6）表现出不同的锂化行为。位置3上的溴很容易发生卤素金属交换。相反，位置6上的溴仅导致C-5取代的衍生物进一步产生邻位导向作用。
• Nitration in the imidazo[1,2-<i>a</i>]pyrazine series. Experimental and computational results
  作者：Olivier Vitse、Pierre-Antoine Bonnet、Jacques Bompart、Henri Viols、Guy Subra、Jean-Pierre Chapat、Gérard Grassy

  DOI：10.1002/jhet.5570340301

  日期：1997.5

  Nitration was carried out on a series of imidazo[1,2-a]pyrazine derivatives. The reactivities of diversely substituted derivatives and of all positions of substitution were analysed and experimental results compared with 13-nmr data and semi empirical calculations (AMI). Although the unsubstituted heterocycle is highly resistant to nitration, electron-donating groups such as alkoxy or alkylamino on

  在一系列咪唑并[1,2- a ]吡嗪衍生物上进行硝化。分析了不同取代的衍生物和所有取代位置的反应性，并将实验结果与13 nmr数据和半经验计算（AMI）进行了比较。尽管未取代的杂环对硝化具有很高的抵抗力，但供电子基团，例如8位上的烷氧基或烷基氨基，可增强咪唑并[1,2- a ]吡嗪衍生物对亲电取代，特别是硝化的反应性。在13-nmr实验，电子分布和以中性形式计算的分子静电势等密度面与实验结果非常吻合，表明位置3是硝化反应中最活泼的位置。
• Bonnet; Vitse; Benezech, Annales Pharmaceutiques Francaises, 1998, vol. 56, # 4, p. 155 - 159
  作者：Bonnet、Vitse、Benezech、Subra、Fabreguettes、Zanik、Laurent、Michel、Bompart、Chapat

  DOI：——

  日期：——
• Synthesis and antibronchospastic activity of 8-alkoxy- and 8-(alkylamino)imidazo[1,2-a]pyrazines
  作者：Pierre A. Bonnet、Alain Michel、Florence Laurent、Claire Sablayrolles、Eliane Rechencq、Jean C. Mani、Maurice Boucard、Jean P. Chapat

  DOI：10.1021/jm00096a008

  日期：1992.9

  Theophylline still occupies a dominant place in asthma therapy. Unfortunatly its adverse central nervous system (CNS) stimulant effects can dramatically limit its use, and adjustments in the dosage are often needed. We have synthesized a new series of imidazo[1,2-a]pyrazine derivatives which are much more potent bronchodilators than theophylline in vivo and do not exhibit the CNS stimulatory profile. In vitro studies on isolated rat uterus and guinea pig trachea confirm the high potentialities of these derivatives. 6-Bromo-8-(methylamino)imidazo[1,2-a]pyrazine-3-carbonitrile (23) is identified as the most potent compound of the series. As in the case of theophylline, phosphodiesterase inhibition appears unlikely to be the unique mechanism of action of this series of heterocycles.