4-(benzothiophen-5-yl)-2-methyl-7-morpholino-1,2-dihydroisoquinolin-3(4H)-one | 877265-14-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 恶嗪烷类
• 英文名称: 4-(benzothiophen-5-yl)-2-methyl-7-morpholino-1,2-dihydroisoquinolin-3(4H)-one
• 英文别名: 4-benzo[b]thien-5-yl-1,4-dihydro-2-methyl-7-(4-morpholinyl)-3(2H)-Isoquinolinone；4-(1-benzothiophen-5-yl)-2-methyl-7-morpholin-4-yl-1,4-dihydroisoquinolin-3-one
• CAS: 877265-14-0
• 化学式: C₂₂H₂₂N₂O₂S
• 分子量: 378.495
• InChiKey: GOXHALYUPWDLKZ-UHFFFAOYSA-N

物化性质

• 沸点：
  635.0±55.0 °C(Predicted)
• 密度：
  1.283±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.4
• 重原子数：
  27
• 可旋转键数：
  2
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.32
• 拓扑面积：
  61
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  4-(benzothiophen-5-yl)-2-methyl-7-morpholino-1,2-dihydroisoquinolin-3(4H)-one 在 dimethyl sulfide borane 、 盐酸 、 sodium hydroxide 作用下， 以 四氢呋喃 、 水 为溶剂， 反应 1.0h， 以66%的产率得到4-(4-(benzothiophen-5-yl)-2-methyl-1,2,3,4-tetrahydroisoquinolin-7-yl)morpholine
  参考文献：
  名称：

  Initial Process Development and Scale-Up of the Synthesis of a Triple Reuptake Inhibitor ALB 109780

  摘要：

  Early process development toward a triple reuptake inhibitor is described. Three different routes were evaluated; one of them was optimized and scaled up to generate 470 g of API as this route minimized the formation of undesired side products. The selected route featured Eaton's reagent-mediated cyclization of a phenyl acetamide, copper-mediated Buchwald Hartwig coupling to install a morpholine moiety, and palladium-catalyzed alpha-arylation of a dihydroisoquinolinone to construct the core structure.

  DOI：

  10.1021/op3000064
• 作为产物：
  描述：

  2-(4-溴苯基)-N-甲基乙酰胺 在 copper(l) iodide 、 磷酸 、 palladium diacetate 、 potassium carbonate 、 R-(+)-1,1'-联萘-2,2'-双二苯膦 、 L-脯氨酸 、 sodium t-butanolate 作用下， 以 1,4-二氧六环 、 二甲基亚砜 为溶剂， 反应 30.0h， 生成 4-(benzothiophen-5-yl)-2-methyl-7-morpholino-1,2-dihydroisoquinolin-3(4H)-one
  参考文献：
  名称：

  Initial Process Development and Scale-Up of the Synthesis of a Triple Reuptake Inhibitor ALB 109780

  摘要：

  Early process development toward a triple reuptake inhibitor is described. Three different routes were evaluated; one of them was optimized and scaled up to generate 470 g of API as this route minimized the formation of undesired side products. The selected route featured Eaton's reagent-mediated cyclization of a phenyl acetamide, copper-mediated Buchwald Hartwig coupling to install a morpholine moiety, and palladium-catalyzed alpha-arylation of a dihydroisoquinolinone to construct the core structure.

  DOI：

  10.1021/op3000064