4-{[(2'S,3'R,4'S,5'R)-6-chloro-4'-(3-chloro-2-fluorophenyl)-2'-(2,2-dimethylpropyl)-2-oxo-1,2-dihydrospiro[indole-3,3'-pyrrolidine]-5'-carbonyl]amino}-3-methoxybenzoic acid dimethyl-((R)-1-phenylethyl)amine salt | 1419186-29-0

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 4-{[(2'S,3'R,4'S,5'R)-6-chloro-4'-(3-chloro-2-fluorophenyl)-2'-(2,2-dimethylpropyl)-2-oxo-1,2-dihydrospiro[indole-3,3'-pyrrolidine]-5'-carbonyl]amino}-3-methoxybenzoic acid dimethyl-((R)-1-phenylethyl)amine salt
• 英文别名: 4-((2'S,3'R,4'S,5'R)-6-chloro-4'-(3-chloro-2-fluorophenyl)-2'-neopentyl-2-oxospiro[indoline-3,3'-pyrrolidine]-5'-carboxamido)-3-methoxybenzoic acid-(R)-N,N-dimethyl-1-phenyl-1-ethylamine；4-[[(2'R,3R,3'S,5'S)-6-chloro-3'-(3-chloro-2-fluorophenyl)-5'-(2,2-dimethylpropyl)-2-oxospiro[1H-indole-3,4'-pyrrolidine]-2'-carbonyl]amino]-3-methoxybenzoic acid;(1R)-N,N-dimethyl-1-phenylethanamine
• CAS: 1419186-29-0
• 化学式: C₁₀H₁₅N*C₃₁H₃₀Cl₂FN₃O₅
• 分子量: 763.737
• InChiKey: HWROTQBWKMAOCT-PKIWXQOZSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  8.54
• 重原子数：
  53
• 可旋转键数：
  9
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.34
• 拓扑面积：
  120
• 氢给体数：
  4
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  4-{[(2'S,3'R,4'S,5'R)-6-chloro-4'-(3-chloro-2-fluorophenyl)-2'-(2,2-dimethylpropyl)-2-oxo-1,2-dihydrospiro[indole-3,3'-pyrrolidine]-5'-carbonyl]amino}-3-methoxybenzoic acid dimethyl-((R)-1-phenylethyl)amine salt 在 ammonium hydroxide 作用下， 以 四氢呋喃 为溶剂， 反应 2.0h， 生成 (2'S,3'R,4'S,5'R)-6-chloro-4'-(3-chloro-2-fluorophenyl)-2'-(2,2-dimethylpropyl)-2-oxo-1,2-dihydrospiro[indole-3,3'-pyrrolidine]-5'-carboxylic acid (4-carbamoyl-2-methoxyphenyl)amide
  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
• 作为产物：
  描述：

  3-甲氧基-4-氨基苯甲酸甲酯 在 N-甲基吗啉 、 C₅₂H₄₄F₁₂FeO₂P₂ 、 silver(I) acetate 、 1-丙基磷酸酐 、 三乙胺 、 sodium hydroxide 作用下， 以 四氢呋喃 、 甲基叔丁基醚 、 水 、 乙酸乙酯 、 甲苯 为溶剂， 反应 59.5h， 生成 4-{[(2'S,3'R,4'S,5'R)-6-chloro-4'-(3-chloro-2-fluorophenyl)-2'-(2,2-dimethylpropyl)-2-oxo-1,2-dihydrospiro[indole-3,3'-pyrrolidine]-5'-carbonyl]amino}-3-methoxybenzoic acid dimethyl-((R)-1-phenylethyl)amine salt
  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

文献信息

• 螺环吲哚酮聚乙二醇碳酸酯类化合物和其组 合物、制备方法及用途
  申请人：肖飞

  公开号：CN107698598B

  公开（公告）日：2019-06-21

  本发明涉及螺环吲哚酮聚乙二醇碳酸酯类化合物、其组合物、制备方法以及其具有抗肿瘤活性而作为抗癌药物的用途。所述螺环吲哚酮聚乙二醇碳酸酯类化合物结构式如下，其具有优异的肿瘤抑制活性，水溶解性好，毒性低，可用于静脉注射剂型。
• EP3498712
  申请人：——

  公开号：——

  公开（公告）日：——
• Synthesis of a Spiroindolinone Pyrrolidinecarboxamide MDM2 Antagonist
  作者：Lianhe Shu、Zizhong Li、Chen Gu、Dan Fishlock

  DOI：10.1021/op3003213

  日期：2013.2.15

  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.