2-(呋喃-2-基)-6-甲基苯并[d]恶唑 | 1021439-34-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并恶唑类
• 中文名称: 2-(呋喃-2-基)-6-甲基苯并[d]恶唑
• 英文名称: 2-(2-furyl)-6-methylbenzoxazole
• 英文别名: 2-(Furan-2-yl)-6-methyl-1,3-benzoxazole；2-(furan-2-yl)-6-methyl-1,3-benzoxazole
• CAS: 1021439-34-8
• 化学式: C₁₂H₉NO₂
• 分子量: 199.209
• InChiKey: LUQUUTHGHASXAQ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.9
• 重原子数：
  15
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.08
• 拓扑面积：
  39.2
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  2-(呋喃-2-基)-6-甲基苯并[d]恶唑 在 N-溴代丁二酰亚胺(NBS) 、 三乙胺 、 过氧化苯甲酰 作用下， 以 四氯化碳 、 丙酮 为溶剂， 反应 4.5h， 生成 2-(furan-2-yl)-6-(piperidin-1-ylmethyl)-1,3-benzoxazole hydrochloride
  参考文献：
  名称：

  Design, synthesis and evaluation of 2-aryl benzoxazoles as promising hit for the A_2Areceptor

  摘要：

  The development of adenosine A_2A receptor antagonists has received much interest in recent years for the treatment of neurodegenerative diseases. Based on docking studies, a new series of 2-arylbenzoxazoles has been identified as potential A_2AR antagonists. Structure-affinity relationship was investigated in position 2, 5 and 6 of the benzoxazole heterocycle leading to compounds with a micromolar affinity towards the A_2A receptor. Compound F1, with an affinity of 1 μm, presented good absorption, distribution, metabolism and excretion properties with an excellent aqueous solubility (184 μm) without being cytotoxic at 100 μm. This compound, along with low-molecular weight compound D1 (K_i = 10 μm), can be easily modulated and thus considered as relevant starting points for further hit-to-lead optimisation.

  DOI：

  10.1080/14756366.2017.1334648
• 作为产物：
  描述：

  N-(2-hydroxy-4-methylphenyl)furan-2-carboxamide 在 对甲苯磺酸 作用下， 以 甲苯 为溶剂， 反应 17.0h， 以68%的产率得到2-(呋喃-2-基)-6-甲基苯并[d]恶唑
  参考文献：
  名称：

  Design, synthesis and evaluation of 2-aryl benzoxazoles as promising hit for the A_2Areceptor

  摘要：

  The development of adenosine A_2A receptor antagonists has received much interest in recent years for the treatment of neurodegenerative diseases. Based on docking studies, a new series of 2-arylbenzoxazoles has been identified as potential A_2AR antagonists. Structure-affinity relationship was investigated in position 2, 5 and 6 of the benzoxazole heterocycle leading to compounds with a micromolar affinity towards the A_2A receptor. Compound F1, with an affinity of 1 μm, presented good absorption, distribution, metabolism and excretion properties with an excellent aqueous solubility (184 μm) without being cytotoxic at 100 μm. This compound, along with low-molecular weight compound D1 (K_i = 10 μm), can be easily modulated and thus considered as relevant starting points for further hit-to-lead optimisation.

  DOI：

  10.1080/14756366.2017.1334648

文献信息

• Copper-Catalyzed Domino Annulation Approaches to the Synthesis of Benzoxazoles under Microwave-Accelerated and Conventional Thermal Conditions
  作者：Russell D. Viirre、Ghotas Evindar、Robert A. Batey

  DOI：10.1021/jo702145d

  日期：2008.5.1

  Two domino annulation approaches for benzoxazole synthesis have been developed. In the first approach, copper-catalyzed intermolecular cross-coupling of 1,2-dihaloarenes with primary amides initially forms the Ar−N bond of the benzoxazole ring, followed by copper-catalyzed intramolecular cyclization to form the Ar−O bond. Benzoxazoles were formed in good yields for the reaction of 1,2-dibromobenzene

  已经开发了两种用于苯并恶唑合成的多米诺环化方法。在第一种方法中，铜催化的1,2-二卤代芳烃与伯酰胺的分子间交叉偶联最初形成苯并恶唑环的Ar-N键，然后进行铜催化的分子内环化形成Ar-O键。苯并恶唑以高产率形成，用于1，2-二溴苯的反应，但该反应对3，4-二溴甲苯的反应没有区域选择性。此外，该方法受到1,2-二卤代芳烃的可用性的限制。由于这些局限性，开发了另一种更通用的单锅多米诺环化策略，该策略涉及在Cs 2 CO 3存在下2-溴苯胺与酰氯的反应。，催化CuI和不可酰化的配体1,10-菲咯啉。在这些条件下，先将苯胺酰化，然后进行铜催化的分子内环化反应，生成2-卤代苯胺，形成苯并恶唑环的Ar-O键。与常规加热相比，使用微波辐射的优化条件获得的反应时间短得多（即210°C持续15分钟，而95°C持续24 h），并被用于合成小型苯并恶唑库。这些铜催化的方法补充了苯并恶唑合成的现有策略，该策略通常利用2-氨基苯酚作为前体。
• Direct transition-metal-free intramolecular C–O bond formation: synthesis of benzoxazole derivatives
  作者：Jinsong Peng、Cuijuan Zong、Min Ye、Tonghui Chen、Dewei Gao、Yufeng Wang、Chunxia Chen

  DOI：10.1039/c0ob00454e

  日期：——

  A direct base-mediated intramolecular carbon-oxygen bond formation has been developed without a transition-metal catalyst. In the presence of 2.0 equiv of K2CO3 in DMSO at 140 °C, the intramolecular cyclization of o-haloanilides affords benzoxazoles in high yields. A mechanism via an initial formation of a benzyne intermediate followed by nucleophilic addition to form the C–O bond has been proposed.

  在不使用过渡金属催化剂的情况下，我们开发出了一种直接由碱介导的分子内碳氧键形成方法。在二甲基亚砜（DMSO）中加入 2.0 等量的 K2CO3，温度为 140 °C，邻卤代苯胺的分子内环化反应能以高产率生成苯并恶唑。提出的机理是先形成苄基中间体，然后通过亲核加成形成 CâO 键。
• Ligand-promoted, copper nanoparticles catalyzed one-pot synthesis of substituted benzoxazoles from 2-bromoanilines and acyl chlorides
  作者：Yong Wang、Chaolong Wu、Shoujie Nie、Dingjian Xu、Min Yu、Xiaoquan Yao

  DOI：10.1016/j.tetlet.2015.10.078

  日期：2015.12

  A facile, highly efficient, and practical one-pot synthetic strategy for benzoxazoles was developed by using copper nanoparticles as a catalyst with o-bromoanilines and acyl chlorides as starting materials. With the promotion of 1,10-phenanthroline ligand, the copper nanoparticles catalyst showed highly catalytic activity under mild conditions. This methodology is tolerant of a wide variety of functional groups and gives good to excellent yields in most examples. Furthermore, the solid catalyst could be recovered and reused conveniently several times with satisfactory yields. (C) 2015 Elsevier Ltd. All rights reserved.
• Design, synthesis and evaluation of 2-aryl benzoxazoles as promising hit for the A_2Areceptor
  作者：Romain Duroux、Nicolas Renault、Joana Esteves Cuelho、Laurence Agouridas、David Blum、Luisa V. Lopes、Patricia Melnyk、Saïd Yous

  DOI：10.1080/14756366.2017.1334648

  日期：2017.1.1

  The development of adenosine A_2A receptor antagonists has received much interest in recent years for the treatment of neurodegenerative diseases. Based on docking studies, a new series of 2-arylbenzoxazoles has been identified as potential A_2AR antagonists. Structure-affinity relationship was investigated in position 2, 5 and 6 of the benzoxazole heterocycle leading to compounds with a micromolar affinity towards the A_2A receptor. Compound F1, with an affinity of 1 μm, presented good absorption, distribution, metabolism and excretion properties with an excellent aqueous solubility (184 μm) without being cytotoxic at 100 μm. This compound, along with low-molecular weight compound D1 (K_i = 10 μm), can be easily modulated and thus considered as relevant starting points for further hit-to-lead optimisation.