(4aS,6S,8aR)-6-(2,5-difluorophenyl)-1-(4-methoxybenzyl)-6-{[4-(trifluoromethyl)phenyl]sulfonyl}octahydro-1H-2,1-benzothiazine 2,2-dioxide | 886061-02-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并噻嗪类
• 英文名称: (4aS,6S,8aR)-6-(2,5-difluorophenyl)-1-(4-methoxybenzyl)-6-{[4-(trifluoromethyl)phenyl]sulfonyl}octahydro-1H-2,1-benzothiazine 2,2-dioxide
• 英文别名: (4aalpha,8aalpha)-1-(4-Methoxybenzyl)-6alpha-(2,5-difluorophenyl)-6-[[4-(trifluoromethyl)phenyl]sulfonyl]octahydro-1H-2,1-benzothiazine 2,2-dioxide；(4aS,6S,8aR)-6-(2,5-difluorophenyl)-1-[(4-methoxyphenyl)methyl]-6-[4-(trifluoromethyl)phenyl]sulfonyl-4,4a,5,7,8,8a-hexahydro-3H-benzo[c]thiazine 2,2-dioxide
• CAS: 886061-02-5
• 化学式: C₂₉H₂₈F₅NO₅S₂
• 分子量: 629.669
• InChiKey: YUMKOBKBDCXQJV-UASRBLEQSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.6
• 重原子数：
  42
• 可旋转键数：
  6
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  97.5
• 氢给体数：
  0
• 氢受体数：
  11

反应信息

• 作为反应物：
  描述：

  (4aS,6S,8aR)-6-(2,5-difluorophenyl)-1-(4-methoxybenzyl)-6-{[4-(trifluoromethyl)phenyl]sulfonyl}octahydro-1H-2,1-benzothiazine 2,2-dioxide 在 甲烷磺酸 、 sodium hexamethyldisilazane 、 巯基乙酸 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 1.83h， 生成 (3R,4aS,6S,8aR)-6-(2,5-difluorophenyl)-3-ethyl-6-{[4-(trifluoromethyl)phenyl]sulfonyl}octahydro-1H-2,1-benzothiazine 2,2-dioxide
  参考文献：
  名称：

  Practical Asymmetric Synthesis of a γ-Secretase Inhibitor Exploiting Substrate-Controlled Intramolecular Nitrile Oxide−Olefin Cycloaddition

  摘要：

  A practical asymmetric synthesis of the gamma-secretase inhibitor (-)-1 is described. As the key transformation, a highly diastereoselective intramolecular nitrile oxide cycloaddition forms the hexahydrobenzisoxazole core of 3 in four operations. Other aspects of the route include a highly stereoselective reduction of an isoxazole to form a cis-gamma-amino alcohol, an efficient chemical resolution, a dianion cyclization to construct a sultam ring, and the alpha-alkylation of a sultam with excellent diastereoselectivity. In each instance, the relative stereochemistry was evolved by way of substrate-based induction with >= 96% ds. Kilogram quantities of the targeted drug candidate (-)-1 were obtained, without recourse to chromatography, by way of 10 isolated intermediates and in 13% overall yield.

  DOI：

  10.1021/jo060033i
• 作为产物：
  描述：

  (2S,4S)-4-(2,5-difluorophenyl)-2-prop-2-enyl-4-[4-(trifluoromethyl)phenyl]sulfonylcyclohexan-1-one 在 氧气 、 氯 、 sodium hydride 、 溶剂黄146 、 三乙胺 作用下， 以 甲醇 、 乙醇 、 二氯甲烷 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 28.01h， 生成 (4aS,6S,8aR)-6-(2,5-difluorophenyl)-1-(4-methoxybenzyl)-6-{[4-(trifluoromethyl)phenyl]sulfonyl}octahydro-1H-2,1-benzothiazine 2,2-dioxide
  参考文献：
  名称：

  WO2006/123183

  摘要：

  公开号：

文献信息

• Sulphone Derivatives for Treatment of Cancer
  申请人：Lewis Huw David

  公开号：US20090306058A1

  公开（公告）日：2009-12-10

  Compounds of Formula (I) are disclosed for treatment of cancer.

  公式（I）的化合物被揭示用于治疗癌症。
• WO2006/123183
  申请人：——

  公开号：——

  公开（公告）日：——
• Practical Asymmetric Synthesis of a γ-Secretase Inhibitor Exploiting Substrate-Controlled Intramolecular Nitrile Oxide−Olefin Cycloaddition
  作者：Jeremy P. Scott、Steven F. Oliver、Karel M. J. Brands、Sarah E. Brewer、Antony J. Davies、Andrew D. Gibb、David Hands、Stephen P. Keen、Faye J. Sheen、Robert A. Reamer、Robert D. Wilson、Ulf-H. Dolling

  DOI：10.1021/jo060033i

  日期：2006.4.1

  A practical asymmetric synthesis of the gamma-secretase inhibitor (-)-1 is described. As the key transformation, a highly diastereoselective intramolecular nitrile oxide cycloaddition forms the hexahydrobenzisoxazole core of 3 in four operations. Other aspects of the route include a highly stereoselective reduction of an isoxazole to form a cis-gamma-amino alcohol, an efficient chemical resolution, a dianion cyclization to construct a sultam ring, and the alpha-alkylation of a sultam with excellent diastereoselectivity. In each instance, the relative stereochemistry was evolved by way of substrate-based induction with >= 96% ds. Kilogram quantities of the targeted drug candidate (-)-1 were obtained, without recourse to chromatography, by way of 10 isolated intermediates and in 13% overall yield.