di-(1-methyl-2-oxoindolin-5-yl) disulphide | 166883-21-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吲哚及其衍生物
• 英文名称: di-(1-methyl-2-oxoindolin-5-yl) disulphide
• 英文别名: 5,5'-Disulfanediylbis(1-methyl-1,3-dihydro-2H-indol-2-one)；1-methyl-5-[(1-methyl-2-oxo-3H-indol-5-yl)disulfanyl]-3H-indol-2-one
• CAS: 166883-21-2
• 化学式: C₁₈H₁₆N₂O₂S₂
• 分子量: 356.469
• InChiKey: BMXOQJZCLXWKFT-UHFFFAOYSA-N

物化性质

• 沸点：
  699.6±55.0 °C(Predicted)
• 密度：
  1.46±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.1
• 重原子数：
  24
• 可旋转键数：
  3
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.22
• 拓扑面积：
  91.2
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  di-(1-methyl-2-oxoindolin-5-yl) disulphide 在 硫酸 、 正己基锂 、 三乙胺 作用下， 以 四氢呋喃 、 正己烷 、 水 、 甲苯 、 乙腈 为溶剂， 反应 65.25h， 生成 5-[[4-[(2S,4R)-4-hydroxy-2-methyl-tetrahydropyran-4-yl]-2-thienyl]sulfanyl]-1-methyl-indolin-2-one
  参考文献：
  名称：

  Efficient Syntheses of AZD4407 via Thioether Formation by Nucleophilic Attack of Organometallic Species on Sulphur

  摘要：

  The development of two efficient strategies for the synthesis of AZD4407 is reported, both of which are considered suitable for large-scale manufacture. In the first approach, 3-bromothiophene is coupled with (2S)-2-methyltetrahydropyran-4one using Grignard chemistry. Following hydroxyl protection and lithiation at thiophene C-2, reaction with a protected 5-mercapto-1-methyl-1,3-dihydro-indol-2-one derivative bearing a leaving group on sulphur provides AZD4407 after acid-catalysed deprotection and epimerisation. The second approach starts from 2,4-dibromothiophene, which undergoes a selective Grignard exchange reaction at C-2 followed by reaction with similar protected mercapto-oxindole derivatives. Reprotection of the oxindole ring, followed by a second Grignard exchange, and reaction with (2S)-2-methyltetrahydropyran-4-one provides AZD4407 after acid-catalysed deprotection and epimerisation.

  DOI：

  10.1021/op0500483
• 作为产物：
  描述：

  1-甲基-2-氧代-5-吲哚啉磺酰氯 在 氢碘酸 作用下， 以200 kg的产率得到di-(1-methyl-2-oxoindolin-5-yl) disulphide
  参考文献：
  名称：

  Efficient Syntheses of AZD4407 via Thioether Formation by Nucleophilic Attack of Organometallic Species on Sulphur

  摘要：

  The development of two efficient strategies for the synthesis of AZD4407 is reported, both of which are considered suitable for large-scale manufacture. In the first approach, 3-bromothiophene is coupled with (2S)-2-methyltetrahydropyran-4one using Grignard chemistry. Following hydroxyl protection and lithiation at thiophene C-2, reaction with a protected 5-mercapto-1-methyl-1,3-dihydro-indol-2-one derivative bearing a leaving group on sulphur provides AZD4407 after acid-catalysed deprotection and epimerisation. The second approach starts from 2,4-dibromothiophene, which undergoes a selective Grignard exchange reaction at C-2 followed by reaction with similar protected mercapto-oxindole derivatives. Reprotection of the oxindole ring, followed by a second Grignard exchange, and reaction with (2S)-2-methyltetrahydropyran-4-one provides AZD4407 after acid-catalysed deprotection and epimerisation.

  DOI：

  10.1021/op0500483

文献信息

• Efficient Syntheses of AZD4407 via Thioether Formation by Nucleophilic Attack of Organometallic Species on Sulphur
  作者：Marie-Lyne Alcaraz、Stéphanie Atkinson、Philip Cornwall、Alison C. Foster、Duncan M. Gill、Lesley A. Humphries、Philip S. Keegan、Richard Kemp、Eric Merifield、Robert A. Nixon、Allison J. Noble、Darren O'Beirne、Zakariya M. Patel、Jacob Perkins、Paul Rowan、Paul Sadler、John T. Singleton、James Tornos、Andrew J. Watts、Ian A. Woodland

  DOI：10.1021/op0500483

  日期：2005.9.1

  The development of two efficient strategies for the synthesis of AZD4407 is reported, both of which are considered suitable for large-scale manufacture. In the first approach, 3-bromothiophene is coupled with (2S)-2-methyltetrahydropyran-4one using Grignard chemistry. Following hydroxyl protection and lithiation at thiophene C-2, reaction with a protected 5-mercapto-1-methyl-1,3-dihydro-indol-2-one derivative bearing a leaving group on sulphur provides AZD4407 after acid-catalysed deprotection and epimerisation. The second approach starts from 2,4-dibromothiophene, which undergoes a selective Grignard exchange reaction at C-2 followed by reaction with similar protected mercapto-oxindole derivatives. Reprotection of the oxindole ring, followed by a second Grignard exchange, and reaction with (2S)-2-methyltetrahydropyran-4-one provides AZD4407 after acid-catalysed deprotection and epimerisation.