(4-difluoromethoxy-3-pyridin-2-ylethynyl-phenyl)-(5,7-dihydro-pyrrolo[3,4-b]pyridin-6-yl)-methanone | 1253291-12-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯并吡啶类
• 英文名称: (4-difluoromethoxy-3-pyridin-2-ylethynyl-phenyl)-(5,7-dihydro-pyrrolo[3,4-b]pyridin-6-yl)-methanone
• 英文别名: [4-(difluoromethoxy)-3-(2-pyridin-2-ylethynyl)phenyl]-(5,7-dihydropyrrolo[3,4-b]pyridin-6-yl)methanone
• CAS: 1253291-12-1
• 化学式: C₂₂H₁₅F₂N₃O₂
• 分子量: 391.377
• InChiKey: JITMSIRHBAVREW-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  29
• 可旋转键数：
  5
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.14
• 拓扑面积：
  55.3
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  4-(二氟甲氧基)-3-碘苯甲酸甲酯 在 bis-triphenylphosphine-palladium(II) chloride 、 ammonium hydroxide 、 copper(l) iodide 、 N,N-二异丙基乙胺 、 N,N'-羰基二咪唑 、 sodium hydroxide 作用下， 以 N-甲基吡咯烷酮 、 甲醇 、 水 为溶剂， 反应 11.5h， 生成 (4-difluoromethoxy-3-pyridin-2-ylethynyl-phenyl)-(5,7-dihydro-pyrrolo[3,4-b]pyridin-6-yl)-methanone
  参考文献：
  名称：

  用S-（二氟甲基）盐对苯酚和硫酚进行二氟甲基化：反应，作用域和机理研究。

  摘要：

  描述了一种用于苯酚和硫酚的二氟甲基化的简便实用方法。利用最近开发的稳定的S-（二氟甲基）ulf盐作为二氟卡宾的前体，在氢氧化锂的存在下，很容易将各种不同官能化的苯酚和硫酚以良好或优异的收率转化为其相应的芳基二氟甲基醚。 。系统地研究了各种O，S-亲核试剂对二氟卡宾的化学选择性，表明反应顺序为ArS-> RS-，ArO-> ROH> RO-，ArSH，ArOH，RSH。

  DOI：

  10.1021/acs.joc.9b02424

文献信息

• [EN] BISARYL ALKYNYLAMIDES AS NEGATIVE ALLOSTERIC MODULATORS OF METABOTROPIC GLUTAMATE RECEPTOR 5 (MGLUR5)<br/>[FR] BISARYL ALCYNYLAMIDES EN TANT QUE MODULATEURS ALLOSTÉRIQUES NÉGATIFS DU RÉCEPTEUR MÉTABOTROPIQUE DU GLUTAMATE 5 (MGLUR5)
  申请人：WYETH LLC

  公开号：WO2010124047A1

  公开（公告）日：2010-10-28

  Disclosed are compounds of Formula (I): pharmaceutical compositions containing compounds of Formula I, and the use of compounds of Formula (I) to treat diseases and disorders including schizophrenia, paranoia, depression, manic-depressive illness and anxiety wherein W1-W5, X1-X4, Y, Z1-Z5, m, n, p, and R1-R6 in Formula (I) are defined in the specification.

  揭示了化合物的公式(I)：包含公式I化合物的药物组合物，以及使用公式(I)化合物治疗包括精神分裂症、偏执狂、抑郁症、躁郁症和焦虑症在内的疾病和紊乱，其中在公式(I)中W1-W5、X1-X4、Y、Z1-Z5、m、n、p和R1-R6的定义在规范中确定。
• Bisaryl Alkynylamides as Negative Allosteric Modulators of Metabotropic Glutamate Receptor 5 (MGLUR5)
  申请人：O'Neil Steven Victor

  公开号：US20100273772A1

  公开（公告）日：2010-10-28

  Disclosed are compounds of Formula I: pharmaceutical compositions containing compounds of Formula I, and the use of compounds of Formula I to treat diseases and disorders including schizophrenia, paranoia, depression, manic-depressive illness and anxiety wherein W 1 -W 5 , X 1 -X 4 , Y, Z 1 -Z 5 , m, n, p, and R 1 -R 6 in Formula I are defined in the specification.

  本发明披露了I式化合物：含有I式化合物的制药组合物，以及使用I式化合物治疗包括精神分裂症、偏执症、抑郁症、躁郁症和焦虑症等疾病和障碍的方法，其中在I式中，W1-W5、X1-X4、Y、Z1-Z5、m、n、p和R1-R6在说明书中有定义。
• Negative allosteric modulators of MGLUR5 for use in the treatment of mature brain damages
  申请人：Sinntaxis AB

  公开号：US11033545B2

  公开（公告）日：2021-06-15

  The present disclosure relates to the use of negative allosteric modulators (NAMs) of the metabotropic glutamate receptor 5 (mGluR5) in the treatment of a mature brain damage, such as damage after stroke.

  本公开涉及代谢型谷氨酸受体 5（mGluR5）的负变构调节剂（NAMs）在治疗成熟脑损伤（如中风后的损伤）中的应用。
• A Robust Process for an mGluR5 Negative Allosteric Modulator: Difluoromethylation and Sonogashira Coupling on Large Scale
  作者：Jeffrey B. Sperry、Roger M. Farr、Mahmut Levent、Mousumi Ghosh、Steven M. Hoagland、Richard J. Varsolona、Karen Sutherland

  DOI：10.1021/op3002728

  日期：2012.11.16

  The development of the potent and selective mGluR5 negative allosteric modulator (NAM) 1 is described. Key features in the process, which has been implemented on a multikilogram scale, include a high-temperature difluoromethylation reaction, a Sonogashira coupling, and careful control of residual Pd and Cu in the final API. Due to the relative nonpolar nature of the intermediates, water-miscible solvents were employed in all four steps to allow for direct crystallizations upon reaction completion. In addition, several crystalline morphologies of the API were discovered, and the isolation of the desired form II will be discussed.
• Difluoromethylation of Phenols and Thiophenols with the <i>S</i>-(Difluo-romethyl)sulfonium Salt: Reaction, Scope, and Mechanistic Study
  作者：Guo-Kai Liu、Wen-Bing Qin、Xin Li、Li-Ting Lin、Henry N. C. Wong

  DOI：10.1021/acs.joc.9b02424

  日期：2019.12.20

  A facile and practical approach for the difluoromethylation of phenols and thiophenols was described. Making use of the recently developed bench-stable S-(difluoromethyl)sulfonium salt as the difluorocarbene precursor, a wide variety of diversely functionalized phenols and thiophenols were readily converted to their corresponding aryl difluoromethyl ethers in good to excellent yields in the presence

  描述了一种用于苯酚和硫酚的二氟甲基化的简便实用方法。利用最近开发的稳定的S-（二氟甲基）ulf盐作为二氟卡宾的前体，在氢氧化锂的存在下，很容易将各种不同官能化的苯酚和硫酚以良好或优异的收率转化为其相应的芳基二氟甲基醚。 。系统地研究了各种O，S-亲核试剂对二氟卡宾的化学选择性，表明反应顺序为ArS-> RS-，ArO-> ROH> RO-，ArSH，ArOH，RSH。