diethyl (R)-2-((3-(6,8-difluorochroman-3-yl)-2-thioxo-2,3-dihydro-1H-imidazol-4-yl)methyl)malonate | 1044769-21-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并吡喃
• 英文名称: diethyl (R)-2-((3-(6,8-difluorochroman-3-yl)-2-thioxo-2,3-dihydro-1H-imidazol-4-yl)methyl)malonate
• CAS: 1044769-21-2
• 化学式: C₂₀H₂₂F₂N₂O₅S
• 分子量: 440.468
• InChiKey: JIYIUFHYANRHJJ-CQSZACIVSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.28
• 重原子数：
  30.0
• 可旋转键数：
  7.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.45
• 拓扑面积：
  82.55
• 氢给体数：
  1.0
• 氢受体数：
  7.0

反应信息

• 作为反应物：
  描述：

  diethyl (R)-2-((3-(6,8-difluorochroman-3-yl)-2-thioxo-2,3-dihydro-1H-imidazol-4-yl)methyl)malonate 在 盐酸 、 甲酸 、 叠氮磷酸二苯酯 、 水 、 三乙胺 、 sodium hydroxide 作用下， 以 1,4-二氧六环 、 甲醇 、 水 、 乙酸乙酯 为溶剂， 反应 12.0h， 生成 依他米司特盐酸盐
  参考文献：
  名称：

  Process Research for Multikilogram Production of Etamicastat: A Novel Dopamine β-Hydroxylase Inhibitor

  摘要：

  In order to develop a manufacturing route to etamicastat, three synthetic approaches to the pivotal chiral 3-aminochroman intermediate have been studied as well as four methods for the construction of the 2-aminoethyl imidazolethione fragment. The evolution of the synthetic strategy based on the early discovery route was described. By focusing on the use of readily available starting materials it was possible to avoid chromatography steps and expensive reagents, bringing about significant improvements in cost and throughput. The best route involves construction of the chiral centre by asymmetric hydrogenation.

  DOI：

  10.1021/op300012d
• 作为产物：
  描述：

  2,4-二氟苯酚 在 三乙烯二胺 、 sodium hypochlorite 、 乌洛托品 、 硫酸 、 水 、 氢气 、 sodium ethanolate 、 溶剂黄146 、 potassium hydroxide 、 sodium hydroxide 作用下， 以 甲醇 、 乙醇 、 溶剂黄146 、 乙酸乙酯 为溶剂， 20.0~115.0 ℃ 、3.0 MPa 条件下， 反应 121.0h， 生成 diethyl (R)-2-((3-(6,8-difluorochroman-3-yl)-2-thioxo-2,3-dihydro-1H-imidazol-4-yl)methyl)malonate
  参考文献：
  名称：

  Process Research for Multikilogram Production of Etamicastat: A Novel Dopamine β-Hydroxylase Inhibitor

  摘要：

  In order to develop a manufacturing route to etamicastat, three synthetic approaches to the pivotal chiral 3-aminochroman intermediate have been studied as well as four methods for the construction of the 2-aminoethyl imidazolethione fragment. The evolution of the synthetic strategy based on the early discovery route was described. By focusing on the use of readily available starting materials it was possible to avoid chromatography steps and expensive reagents, bringing about significant improvements in cost and throughput. The best route involves construction of the chiral centre by asymmetric hydrogenation.

  DOI：

  10.1021/op300012d