2-benzyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)isoquinolin-1-one | 1558050-02-4

• 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-benzyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)isoquinolin-1-one
• CAS: 1558050-02-4
• 化学式: C₂₂H₂₄BNO₃
• 分子量: 361.248
• InChiKey: SPDCPSRARWHQPZ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.35
• 重原子数：
  27.0
• 可旋转键数：
  3.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.32
• 拓扑面积：
  40.46
• 氢给体数：
  0.0
• 氢受体数：
  4.0

反应信息

• 作为反应物：
  描述：

  2-benzyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)isoquinolin-1-one 在 四(三苯基膦)钯 、 sodium carbonate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 生成 methyl 2-(2-methyl-1H-indol-1-yl)acetate
  参考文献：
  名称：

  Discovery of Isoquinolinone Indole Acetic Acids as Antagonists of Chemoattractant Receptor Homologous Molecule Expressed on Th2 Cells (CRTH2) for the Treatment of Allergic Inflammatory Diseases

  摘要：

  Previously we reported the discovery of CRA-898 (1), a diazine indole acetic acid containing CRTH2 antagonist. This compound had good in vitro and in vivo potency, low rates of metabolism, moderate permeability, and good oral bioavailability in rodents. However, it showed low oral exposure in nonrodent safety species (dogs and monkeys). In the current paper, we wish to report our efforts to understand and improve the poor PK in nonrodents and development of a new isoquinolinone subseries that led to identification of a new development candidate, CRA-680 (44). This compound was efficacious in both a house dust mouse model of allergic lung inflammation (40 mg/kg qd) as well as a guinea pig allergen challenge model of lung inflammation (20 mg/kg bid).

  DOI：

  10.1021/jm401509e
• 作为产物：
  描述：

  1-羟基-4-溴异喹啉 在 1,1'-双(二苯膦基)二茂铁二氯化钯(II)二氯甲烷复合物 、 potassium acetate 、 sodium hydride 作用下， 以 二氯甲烷 、 二甲基亚砜 为溶剂， 反应 12.0h， 生成 2-benzyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)isoquinolin-1-one
  参考文献：
  名称：

  Discovery of Isoquinolinone Indole Acetic Acids as Antagonists of Chemoattractant Receptor Homologous Molecule Expressed on Th2 Cells (CRTH2) for the Treatment of Allergic Inflammatory Diseases

  摘要：

  Previously we reported the discovery of CRA-898 (1), a diazine indole acetic acid containing CRTH2 antagonist. This compound had good in vitro and in vivo potency, low rates of metabolism, moderate permeability, and good oral bioavailability in rodents. However, it showed low oral exposure in nonrodent safety species (dogs and monkeys). In the current paper, we wish to report our efforts to understand and improve the poor PK in nonrodents and development of a new isoquinolinone subseries that led to identification of a new development candidate, CRA-680 (44). This compound was efficacious in both a house dust mouse model of allergic lung inflammation (40 mg/kg qd) as well as a guinea pig allergen challenge model of lung inflammation (20 mg/kg bid).

  DOI：

  10.1021/jm401509e

文献信息

• Iridium‐Catalyzed β‐C(sp ² )−H Borylation of Enamides – Access to 3,3‐Dihalogeno‐2‐methoxypiperidines
  作者：Isabelle Gillaizeau、Ismaël Dondasse、Cyril Nicolas、Liliane Mimoun、Volodymyr Sukach、Hervé Meudal

  DOI：10.1002/ejoc.202101302

  日期：2022.1.17

  An efficient iridium-catalyzed C(sp2)−H reaction of non-aromatic tertiary enamides was successfully developed under mild reaction conditions and with high regioselectivity, leading to original C-3 borylated enamides in good yields. These derivatives could then be exploited in Suzuki cross-coupling reactions, or converted into valuable 3,3-dihalogenopiperidine derivatives through short reaction times

  在温和的反应条件和高区域选择性下，成功地开发了一种有效的铱催化的非芳族叔烯酰胺的C( sp 2 )-H 反应，从而以良好的收率得到原始的 C-3 硼化烯酰胺。这些衍生物随后可用于 Suzuki 交叉偶联反应，或通过短反应时间以中等至良好的产率转化为有价值的 3,3-二卤代哌啶衍生物。