2-(4-fluorobenzyl)isoquinolin-1(2H)-one

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 异喹啉及其衍生物
• 英文名称: 2-(4-fluorobenzyl)isoquinolin-1(2H)-one
• 英文别名: 2-[(4-fluorophenyl)methyl]isoquinolin-1-one
• 化学式: C₁₆H₁₂FNO
• 分子量: 253.276
• InChiKey: LBKCHCHTSRLQMS-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  19
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.06
• 拓扑面积：
  20.3
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为产物：
  描述：

  在 盐酸 作用下， 以 1,4-二氧六环 为溶剂， 反应 1.5h， 以87%的产率得到2-(4-fluorobenzyl)isoquinolin-1(2H)-one
  参考文献：
  名称：

  在温和条件下高效快速合成N-取代的异喹啉-1-酮：容易获得花青碱衍生物

  摘要：

  我们描述了N-取代的异喹啉-1-酮衍生物的简单有效的合成。通过将含有乙烯基醚的苯甲酸与不同的胺偶联，然后在室温下在酸性条件下快速分子内环化，可以提供高收率的N-取代异喹啉-1-酮。通过实际合成天然花青素及其类似物，证明了这种简单温和的环化方法的实用性。

  DOI：

  10.1016/j.tetlet.2019.03.073

文献信息

• Iodine-Catalyzed Oxidative Functionalization of Azaarenes with Benzylic C(sp³)–H Bonds via N-Alkylation/Amidation Cascade: Two-Step Synthesis of Isoindolo[2,1-<i>b</i>]isoquinolin-7(5<i>H</i>)-one
  作者：Wen-Kun Luo、Xin Shi、Wang Zhou、Luo Yang

  DOI：10.1021/acs.orglett.6b00646

  日期：2016.5.6

  An efficient and practical iodine-catalyzed oxidative functionalization of azaarenes with benzylic C–H bonds via an N-alkylation and amidation cascade is developed to provide isoquinolin-1(2H)-ones. This method utilizes readily available unfunctionalized azaarenes and methylarenes as starting materials and proceeds under metal-free conditions with good to excellent yields, avoiding the use of expensive

  通过N-烷基化和酰胺化级联反应，开发了一种有效且实用的碘催化的氮杂芳烃与苄基CH键的氧化功能化反应，以提供异喹啉-1（2 H）-one。该方法利用容易获得的未官能化的氮杂芳烃和甲基芳烃作为起始原料，并在无金属条件下以良好或优异的收率进行，避免了使用昂贵的贵金属催化剂以及避免产生卤化物和金属废物。该反应的合成效用以异吲哚并[2,1 - b ]异喹啉-7（5 H）-one的简明两步合成为例。
• Copper-Mediated Oxidative Functionalization of C(sp³)–H Bonds with Isoquinolines: Two-Step Synthesis of 5-Oxaprotoberberinones
  作者：Dingyi Wang、Rongxing Zhang、Ruihong Deng、Sen Lin、Shengmei Guo、Zhaohua Yan

  DOI：10.1021/acs.joc.6b02145

  日期：2016.11.18

  functionalization of C(sp3)–H bonds with isoquinolines via a radical process without ligands was achieved. The present system exhibits a novel pathway for the preparation of N-alkyl (benzyl) isoquinolin-1(2H)-ones in moderate to high yields. In addition, this procedure provides a simple method to afford 5-oxaprotoberberinones and their derivatives in two steps.

  通过没有配体的自由基过程实现了铜介导的C（sp 3）–H键与异喹啉的氧化功能化。本系统展示了以中等至高收率制备N-烷基（苄基）异喹啉-1（2H）-的新颖途径。此外，该程序提供了一种简单的方法，可分两步获得5-氧杂小ber碱和它们的衍生物。
• [EN] NOVEL PYRIDINONE DERIVATIVES AND THEIR USE AS POSITIVE ALLOSTERIC MODULATORS OF MGLUR2-RECEPTORS<br/>[FR] NOUVEAUX DERIVES DE PYRIDINONE ET LEUR UTILISATION EN TANT QUE MODULATEURS ALLOSTERIQUES POSITIFS DES RECEPTEURS MGLUR2
  申请人：JANSSEN PHARMACEUTICA NV

  公开号：WO2006030032A1

  公开（公告）日：2006-03-23

  The present invention relates to novel compounds, in particular novel pyridinone derivat ives according to Formula (I) X R1 N Y (I) R2 R3 wherein all radicals are defined in the application. The compounds according to the invention are positive allosteric modulators of metabotropic receptors - subt ype 2 ('mGluR2') which are useful for the treatment or prevention of neurological and psychiatric disorders associated with glutamate dysfunction and diseases in which the mGluR2 subtype of metabotropic receptors is involved. In particular, such diseases are central nervous system disorders selected from the group of anxiety, schizophrenia, migraine, depression, and epilepsy. The invention is also directed to pharmaceutical compositions and processes to prepare such compounds and compositions, as well as to the use of such compounds for the prevention and treatment of such diseases in which mGluR2 is involved.

  本发明涉及新化合物，特别是根据式（I）X R1 N Y（I）R2 R3定义的新吡啶酮衍生物。根据本发明的化合物是代谢型受体-亚型2（'mGluR2'）的阳性变构调节剂，对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涉及代谢型受体的mGluR2亚型的疾病具有用处。特别是，这些疾病是从焦虑、精神分裂症、偏头痛、抑郁症和癫痫等中枢神经系统障碍组中选择的。该发明还涉及制备此类化合物和组合物的药物组合物和过程，以及利用这类化合物预防和治疗涉及mGluR2的这类疾病。
• Ruthenium-Mediated Dual Catalytic Reactions of Isoquinoline <i>via</i> C−H Activation and Dearomatization for Isoquinolone
  作者：Ting-Hsuan Wang、Wei-Chih Lee、Tiow-Gan Ong

  DOI：10.1002/adsc.201600313

  日期：2016.9.1

  We have unraveled the ruthenium‐promoted prototype reaction based on C(sp2)−C(sp3) bond formation through the reigoselective C−H activation of isoquinoline and pyridine derivatives with various alkyl halides, leading to 1‐substituted isoquinoline products in good yield. This C−H catalytic reaction did not rely on chelation assistance of the directing group of the substrates. The dimer [RuCl2(p‐cymene)]2

  我们已经解开了钌促进的基于C（sp 2）-C（sp 3）键形成的原型反应，该反应是通过对异喹啉和吡啶衍生物与各种卤代烷进行区域选择性C H活化而形成的，从而得到了1取代的异喹啉产品屈服。该CH催化反应不依赖于底物的导向基团的螯合辅助。二聚体[RuCl 2（p- cymene）] 2与N-杂环卡宾配体，金刚烷羧酸和K 2 CO 3碱在N中的结合最佳的条件是在150°C下使用2-甲基-2-吡咯烷酮溶液。同时，我们还能够通过添加水来化学调节反应模式以脱芳香化，从而制得异喹诺酮产品。该反应方法不适用于其他含氮杂芳烃，如哒嗪和嘧啶。
• NOVEL PYRIDINONE DERIVATIVES AND THEIR USE AS POSITIVE ALLOSTERIC MODULATORS OF MGLUR2-RECEPTORS
  申请人：Imogai Julien Hassan

  公开号：US20070213323A1

  公开（公告）日：2007-09-13

  The present invention relates to novel compounds, in particular novel pyridinone derivatives according to Formula (I) X R1 N Y (I) R2 R3 wherein all radicals are defined in the application. The compounds according to the invention are positive allosteric modulators of metabotropic receptors-subtype 2 (“mGluR2”) which are useful for the treatment or prevention of neurological and psychiatric disorders associated with glutamate dysfunction and diseases in which the mGluR2 subtype of metabotropic receptors is involved. In particular, such diseases are central nervous system disorders selected from the group of anxiety, schizophrenia, migraine, depression, and epilepsy. The invention is also directed to pharmaceutical compositions and processes to prepare such compounds and compositions, as well as to the use of such compounds for the prevention and treatment of such diseases in which mGluR2 is involved.

  本发明涉及新型化合物，特别是按照公式（I）X R1 N Y（I）R2 R3定义的新型吡啶酮衍生物。该发明的化合物是代谢型受体亚型2（“mGluR2”）的正向变构调节剂，适用于治疗或预防与谷氨酸功能障碍相关的神经系统和精神障碍以及涉及代谢型受体亚型2的疾病。特别是，这些疾病是选择自焦虑、精神分裂症、偏头痛、抑郁症和癫痫等中枢神经系统疾病的一组。本发明还涉及制备这种化合物和组合物的制药组合物和制备过程，以及利用这种化合物预防和治疗涉及mGluR2的这些疾病的用途。