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 methyl ester | 1419186-30-3

• 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 methyl ester
• 英文别名: methyl 4-((2'S,3R,4'S,5'R)-6-chloro-4'-(3-chloro-2-fluorophenyl)-2'-neopentyl-2-oxospiro[indoline-3,3'-pyrrolidine]-5'-ylcarboxamido)-3-methoxybenzoate；rac-4-{[(2'S,3'R,4'S,5'R)-6-chloro-4'-(3-chloro-2-fluoro-phenyl)-2'-(2,2-dimethyl-propyl)-2-oxo-1,2-dihydro-spiro[indole-3,3'-pyrrolidine]-5'-carbonyl]-amino}-3-methoxy-benzoic acid methyl ester；methyl 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-methoxybenzoate
• CAS: 1419186-30-3
• 化学式: C₃₂H₃₂Cl₂FN₃O₅
• 分子量: 628.528
• InChiKey: OXPQTKXQOBKFHN-AWOIFXJGSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6
• 重原子数：
  43
• 可旋转键数：
  8
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.34
• 拓扑面积：
  106
• 氢给体数：
  3
• 氢受体数：
  7

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 methyl ester 在 ammonium hydroxide 、 sodium hydroxide 作用下， 以 四氢呋喃 、 水 、 乙酸乙酯 为溶剂， 反应 10.0h， 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 、 (6,6’-dimethoxy-[1,1 ‘-biphenyl]-2,2’-diyl)bis(bis(3 ,5-dimethyl-phenyl)phosphine) 、 silver(I) acetate 、 1-丙基磷酸酐 、 三乙胺 作用下， 以 2-甲基四氢呋喃 、 甲基叔丁基醚 、 乙酸乙酯 为溶剂， 反应 31.5h， 生成 rac-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 methyl ester 、 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 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

文献信息

• SPIROINDOLINONE PYRROLIDINES
  申请人：Bartkovitz David Joseph

  公开号：US20110130398A1

  公开（公告）日：2011-06-02

  There are provided compounds of the formula wherein X, Y and R 1 to R 8 are described herein along with the enantiomers, pharmaceutically acceptable salts and esters thereof. The compounds are useful as anticancer agents.

  提供了以下式中的化合物，其中X、Y和R1至R8如本文所述，以及其对映体、药用可接受的盐和酯。这些化合物可用作抗癌药物。
• Substituted Spiro[3H-Indole-3,6'(5'H)-[1H]Pyrrolo[1,2c]Imidazole-1',2(1H,2'H)-diones
  申请人：Chu Xin-Jie

  公开号：US20120071499A1

  公开（公告）日：2012-03-22

  There are provided compounds of the formula wherein X, Y, R 1 , R 1′ , R 2 , R 2′ , R 3 , R 4 , R 5 and R 6 are as described herein and enantiomers or a pharmaceutically acceptable salt or ester thereof. The compounds are useful as anticancer agents.

  提供了具有以下结构的化合物，其中X、Y、R1、R1'、R2、R2'、R3、R4、R5和R6如本文所述，其对映体或药用可接受的盐或酯。这些化合物可用作抗癌剂。
• Spiroindolinone pyrrolidines
  申请人：Hoffman-La Roche Inc.

  公开号：US08088815B2

  公开（公告）日：2012-01-03

  There are provided compounds of the formula wherein X, Y and R1 to R8 are described herein along with the enantiomers, pharmaceutically acceptable salts and esters thereof. The compounds are useful as anticancer agents.

  提供了具有以下式子的化合物，其中X、Y和R1到R8的描述在此提供，还提供它们的对映体、药学上可接受的盐和酯。这些化合物可用作抗癌剂。
• SPIROCYCLIC INDOLONE POLYETHYLENE GLYCOL CARBONATE COMPOUND, COMPOSITION, PREPARATION METHOD AND USE THEREOF
  申请人：Xiao, Fei

  公开号：EP3498712A1

  公开（公告）日：2019-06-19

  The present invention relates to a spirocyclic indolone polyethylene glycol carbonate compound, a composition thereof, a preparation method therefor, and a use thereof as an anticancer drug due to the antitumor activity thereof. The structural formula of the spirocyclic indolone polyethylene glycol carbonate compound is shown below. The compound has excellent tumor inhibitory activity, water solubility, low toxicity, and can be used for intravenous injection.

  本发明涉及一种螺环吲哚酮聚乙二醇碳酸酯化合物、其组合物、其制备方法以及由于其抗肿瘤活性而作为抗癌药物的用途。螺环吲哚酮聚乙二醇碳酸酯化合物的结构式如下所示。该化合物具有优异的肿瘤抑制活性、水溶性、低毒性，可用于静脉注射。
• Spirocyclic indolone polyethylene glycol carbonate compound, composition, preparation method and use thereof
  申请人：Xiao Fei

  公开号：US10471154B2

  公开（公告）日：2019-11-12

  The present invention relates to a spirocyclic indolone polyethylene glycol carbonate compound, a composition thereof, a preparation method therefor, and a use thereof as an anticancer drug due to the antitumor activity thereof. The structural formula of the spirocyclic indolone polyethylene glycol carbonate compound is shown below. The compound has excellent tumor inhibitory activity, water solubility, low toxicity, and can be used for intravenous injection.

  本发明涉及一种螺环吲哚酮聚乙二醇碳酸酯化合物、其组合物、其制备方法以及由于其抗肿瘤活性而作为抗癌药物的用途。螺环吲哚酮聚乙二醇碳酸酯化合物的结构式如下所示。该化合物具有优异的肿瘤抑制活性、水溶性、低毒性，可用于静脉注射。