| 1419186-17-6

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 二芳基庚烷
• CAS: 1419186-17-6
• 化学式: C₁₅H₇Cl₂FN₂O₂
• 分子量: 337.137
• InChiKey: PPFKGTVTQBLMES-UXBLZVDNSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.1
• 重原子数：
  22.0
• 可旋转键数：
  3.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  66.93
• 氢给体数：
  0.0
• 氢受体数：
  3.0

反应信息

• 作为反应物：
  描述：

  、 [3,3-dimethyl-but-(E)-ylideneamino]-acetic acid methyl ester 在 bis(acetylacetonate)oxovanadium 、 platinum on carbon 、 氢气 、 silver(I) acetate 、 三苯基膦 作用下， 以 四氢呋喃 、 甲苯 为溶剂， 20.0 ℃ 、344.75 kPa 条件下， 反应 2.0h， 生成 rac-(2S,3S,3aR,8aR)-6-chloro-3-(3-chloro-2-fluorophenyl)-3a-cyano-8a-(2,2-dimethyl-propyl)-1,2,3,3a,8,8a-hexahydropyrrolo[2,3-b]indole-2-carboxylic acid methyl ester
  参考文献：
  名称：

  Synthesis of a Spiroindolinone Pyrrolidinecarboxamide MDM2 Antagonist

  摘要：

  A practical synthesis of a spiroindolinone pyrrolidinecarboxamide MDM2 antagonist 2 is reported. Cycloaddition of dipolarophile 3 with imine 30 afforded a complex mixture of diastereomers that were isomerized to the desired stereoisomer 31 by heating the mixture in the presence of DBU. After hydrolysis, the resulting product was resolved with a chiral amine to give an enantiopure acid which was converted to the target product 2. The process has been scaled up to a multihundred-gram scale. In addition, an asymmetric synthesis of 31 catalyzed by AgOAc and a chiral phosphine ligand was developed to give enantiomerically enriched 31, which was also converted to enantiopure 2.

  DOI：

  10.1021/op3003213