1-(difluoromethyl)-3-methylbenzene

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 1-(difluoromethyl)-3-methylbenzene
• 化学式: C₈H₈F₂
• 分子量: 142.148
• InChiKey: UNKWTGRKESTOQP-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  10
• 可旋转键数：
  1
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  0
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  1-(difluoromethyl)-3-methylbenzene 、 三(五氟苯基)硼烷 、 三(邻甲基苯基)磷 以 二氯甲烷 为溶剂， 反应 24.0h， 以89%的产率得到
  参考文献：
  名称：

  Selective Monodefluorination and Wittig Functionalization of gem-Difluoromethyl Groups to Generate Monofluoroalkenes

  摘要：

  Monodefluorination of gem-difluoromethyl groups is achieved using a frustrated Lewis pair (FLP) approach. Triarylphosphines and group 13 Lewis acids were surveyed as FLP components, with the combination of P(o-Tol)(3) and B(C6F5)(3) found to provide the best results, although the reaction is feasible with more economical components (PPh3 and BF3 center dot OEt2). The alpha-fluoroalkylphosphonium products arising from the reaction were of lower activity, in regard to further fluoride abstraction, as compared to difluoride starting materials, leading to highly selective monodefluorination. The activated substrates were subject to Wittig reaction protocols to generate a variety of monofluoroalkenes in moderate to high yields.

  DOI：

  10.1021/jacs.8b06770
• 作为产物：
  描述：

  3-甲基苯硼酸频呐醇酯 在 四甲基乙二胺 、 magnesium bromide 、 iron(II) chloride 作用下， 以 四氢呋喃 为溶剂， 反应 2.02h， 生成 1-(difluoromethyl)-3-methylbenzene
  参考文献：
  名称：

  用砜试剂对芳基硼酸酯进行铁催化氟烷基化：超越还原电位的限制

  摘要：

  砜和芳基硼化合物之间的铁催化烷基-芳基偶联反应仍然是一个挑战。我们报告了第一个铁催化的芳基硼酸酯与 N-杂芳基砜的自由基二氟烷基化。铁催化剂与 N-杂芳基砜的氮原子之间的配位被认为对于克服分子间单电子转移过程中砜的还原电位限制很重要，这使得氟烷基 N-杂芳基砜（具有相对较高的还原电位）和非氟化烷基 N-杂芳基砜（具有低还原电位）作为强大的烷基化试剂。

  DOI：

  10.1002/anie.202102597

文献信息

• SUBSTITUTED 4-PYRIDONES AND THEIR USE AS INHIBITORS OF NEUTROPHIL ELASTASE ACTIVITY
  申请人：OOST Thorsten

  公开号：US20140057916A1

  公开（公告）日：2014-02-27

  This invention relates to substituted 4-pyridones of formula 1 and their use as inhibitors of neutrophil elastase activity, pharmaceutical compositions containing the same, and methods of using the same as agents for treatment and/or prevention of pulmonary, gastrointestinal and genitourinary diseases, inflammatory diseases of the skin and the eye and other auto-immune and allergic disorders, allograft rejection, and oncological diseases.

  这项发明涉及式1的取代4-吡啶酮及其作为中性粒细胞弹性蛋白酶活性抑制剂的用途，包含这些化合物的药物组合物，以及将其用作治疗和/或预防肺部、胃肠道和泌尿系统疾病、皮肤和眼睛的炎症性疾病以及其他自身免疫和过敏性疾病、移植物排斥反应和肿瘤性疾病的药剂的方法。
• [EN] SUBSTITUTED BRIDGED UREA ANALOGS AS SIRTUIN MODULATORS<br/>[FR] ANALOGUES D'URÉE PONTÉS SUBSTITUÉS EN TANT QUE MODULATEURS DE SIRTUINE
  申请人：GLAXOSMITHKLINE IP NO 2 LTD

  公开号：WO2016079709A1

  公开（公告）日：2016-05-26

  The present invention relates to novel substituted bridged urea analog compounds of Formula (I) or pharmaceutically acceptable salts thereof, corresponding pharmaceutical compositions, processes for making and use of such compounds, alone or in combination with other therapeutic agents, as Sirtuin Modulators useful for increasing lifespan of a cell, and for use in treating and/or preventing a wide variety of diseases and disorders, which include, but are not limited to, for example, diseases or disorders related to aging or stress, diabetes, obesity, neurodegenerative diseases, cardiovascular disease, blood clotting disorders, inflammation, cancer, and/or flushing as well as diseases or disorders that would benefit from increased mitochondrial activity.

  本发明涉及一种新型的取代桥式脲类似物化合物，其化学式为（I）或其药学上可接受的盐，相应的药物组合物，制备这种化合物的方法以及单独使用或与其他治疗剂联合使用的这些化合物作为Sirtuin调节剂，可用于增加细胞寿命，并用于治疗和/或预防各种疾病和紊乱，包括但不限于与衰老或压力、糖尿病、肥胖、神经退行性疾病、心血管疾病、血液凝块紊乱、炎症、癌症和/或潮红有关的疾病或紊乱，以及那些会受益于增加线粒体活性的疾病或紊乱。
• [EN] SUBSTITUTED BICYCLIC DIHYDROPYRIMIDINONES AND THEIR USE AS INHIBITORS OF NEUTROPHIL ELASTASE ACTIVITY<br/>[FR] DIHYDROPYRIMIDINONES BICYCLIQUES SUBSTITUÉES ET LEUR UTILISATION EN TANT QU'INHIBITEURS DE L'ACTIVITÉ ÉLASTASE DE NEUTROPHILES
  申请人：BOEHRINGER INGELHEIM INT

  公开号：WO2014135414A1

  公开（公告）日：2014-09-12

  This invention relates to substituted bicyclic dihydropyrimidinones of formula (1) and their use as inhibitors of neutrophil elastase activity, pharmaceutical compositions containing the same, and methods of using the same as agents for treatment and/or prevention of pulmonary, gastrointestinal and genitourinary diseases, inflammatory diseases of the skin and the eye and other autoimmune and allergic disorders, allograft rejection, and oncological diseases.

  这项发明涉及式（1）的取代双环二氢嘧啶酮及其作为中性粒细胞弹性蛋白酶活性抑制剂的用途，含有这些化合物的药物组合物，以及将其用作治疗和/或预防肺部、胃肠道和泌尿系统疾病、皮肤和眼睛的炎症性疾病以及其他自身免疫和过敏性疾病、移植物排斥反应和肿瘤性疾病的药剂的方法。
• Iron-Catalyzed Difluoromethylation of Arylzincs with Difluoromethyl 2-Pyridyl Sulfone
  作者：Wenjun Miao、Yanchuan Zhao、Chuanfa Ni、Bing Gao、Wei Zhang、Jinbo Hu

  DOI：10.1021/jacs.7b11976

  日期：2018.1.24

  We report the first iron-catalyzed difluoromethylation of arylzincs with difluoromethyl 2-pyridyl sulfone via selective C-S bond cleavage. This method employs the readily available, bench-stable fluoroalkyl sulfone reagent and inexpensive iron catalyst, allowing facile access to structurally diverse difluoromethylated arenes at low temperatures. The experiment employing a radical clock indicates the

  我们报告了第一次铁催化的芳基锌与二氟甲基 2-吡啶基砜通过选择性 CS 键断裂的二氟甲基化反应。该方法使用容易获得的、工作台稳定的氟代烷基砜试剂和廉价的铁催化剂，可以在低温下轻松获得结构多样的二氟甲基化芳烃。使用自由基时钟的实验表明自由基物种参与了这种铁催化的二氟甲基化过程。
• Modulators of Cystic Fibrosis Transmembrane Conductance Regulator
  申请人：VERTEX PHARMACEUTICALS INCORPORATED

  公开号：US20160095858A1

  公开（公告）日：2016-04-07

  The present invention features a compound of formula I: or a pharmaceutically acceptable salt thereof, where R 1 , R 2 , R 3 , W, X, Y, Z, n, o, p, and q are defined herein, for the treatment of CFTR mediated diseases, such as cystic fibrosis. The present invention also features pharmaceutical compositions, method of treating, and kits thereof.

  本发明涉及一种具有以下化学式I的化合物： 或其药用可接受的盐，其中R 1 ，R 2 ，R 3 ，W，X，Y，Z，n，o，p和q在此处定义，用于治疗CFTR介导的疾病，如囊性纤维化。本发明还涉及药物组合物、治疗方法和相关工具包。