2-[(3R)-7-fluoro-1,2,3,4-tetrahydrocyclopenta[b]indol-3-yl]acetic acid | 800381-16-2

• 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: 2-[(3R)-7-fluoro-1,2,3,4-tetrahydrocyclopenta[b]indol-3-yl]acetic acid
• CAS: 800381-16-2
• 化学式: C₁₃H₁₂FNO₂
• 分子量: 233.242
• InChiKey: IDOLDTCRCJMHBH-SSDOTTSWSA-N

物化性质

• 沸点：
  464.7±40.0 °C(Predicted)
• 密度：
  1.393±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.1
• 重原子数：
  17
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.31
• 拓扑面积：
  53.1
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  2-[(3R)-7-fluoro-1,2,3,4-tetrahydrocyclopenta[b]indol-3-yl]acetic acid 、 sodium methansulfinate 、 4-氯氯苄 生成 S-Laropiprant 、 拉罗皮兰
  参考文献：
  名称：

  An efficient enzyme-catalyzed kinetic resolution: large-scale preparation of an enantiomerically pure indole-ethyl ester derivative, a key component for the synthesis of a prostaglandin D2 receptor antagonist, an anti-allergic rhinitis drug candidate

  摘要：

  Three racemic esters including indole-ethyl ester I as well as its related derivatives 3 and 4 in Scheme 1, all synthetic intermediates for the preparation of chiral compound 5, were used as substrates to evaluate the catalytic potentials of a panel of commercial enzymes for asymmetric hydrolysis. After an extensive evaluation of the conversion rates (C), enantiomeric excesses (ee) and enantioselectivity determination (E), lipase from Pseudomonas fluorescens was identified. This lipase catalyzed the asymmetric hydrolysis of racemic indole-ethyl ester I affording the desired enantiomerically pure intermediate 1 with 97% ee and an E value of 425. Indole-ethyl ester 1, with the following attributes: being early in the synthetic scheme, showing resistance to racemization in the later chemical reactions as well as the possibility of the recycling of the unwanted enantiomer, was therefore selected for optimization and establishment of an enzyme-catalyzed reaction for the industrial-scale synthesis of the compound 5, a drug candidate for the treatment of allergic rhinitis. (C) 2005 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.tetasy.2005.08.021
• 作为产物：
  描述：

  ethyl (3R)-(7-fluoro-1,2,3,4-tetrahydrocyclopenta[b]indol-3-yl)acetate 在 sodium hydroxide 作用下， 生成 2-[(3R)-7-fluoro-1,2,3,4-tetrahydrocyclopenta[b]indol-3-yl]acetic acid
  参考文献：
  名称：

  An efficient enzyme-catalyzed kinetic resolution: large-scale preparation of an enantiomerically pure indole-ethyl ester derivative, a key component for the synthesis of a prostaglandin D2 receptor antagonist, an anti-allergic rhinitis drug candidate

  摘要：

  Three racemic esters including indole-ethyl ester I as well as its related derivatives 3 and 4 in Scheme 1, all synthetic intermediates for the preparation of chiral compound 5, were used as substrates to evaluate the catalytic potentials of a panel of commercial enzymes for asymmetric hydrolysis. After an extensive evaluation of the conversion rates (C), enantiomeric excesses (ee) and enantioselectivity determination (E), lipase from Pseudomonas fluorescens was identified. This lipase catalyzed the asymmetric hydrolysis of racemic indole-ethyl ester I affording the desired enantiomerically pure intermediate 1 with 97% ee and an E value of 425. Indole-ethyl ester 1, with the following attributes: being early in the synthetic scheme, showing resistance to racemization in the later chemical reactions as well as the possibility of the recycling of the unwanted enantiomer, was therefore selected for optimization and establishment of an enzyme-catalyzed reaction for the industrial-scale synthesis of the compound 5, a drug candidate for the treatment of allergic rhinitis. (C) 2005 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.tetasy.2005.08.021

文献信息

• [EN] FLUORO-METHANESULFONYL-SUBSTITUTED CYCLOALKANOINDOLES AND THEIR USE AS PROSTAGLANDIN D2 ANTAGONISTS<br/>[FR] FLUORO-METHANESULFONYL- CYCLOALKANOINDOLES SUBSTITUES ET LEUR UTILISATION EN TANT QU'ANTAGONISTES DE PROSTAGLANDINE D2
  申请人：MERCK FROSST CANADA INC

  公开号：WO2004103970A1

  公开（公告）日：2004-12-02

  Novel cycloalkanoindole derivatives of formula (I) are antagonists of prostaglandins, and as such are useful for the treatment of prostaglandin mediated diseases.

  化合物(I)的新型环烷基吲哚衍生物是前列腺素拮抗剂，因此对于治疗前列腺素介导的疾病是有用的。
• Fluoro-methanesulfonyl-substituted cycloalkanoindoles and their use as prostaglandin D2 antagonists
  申请人：Li Lianhai

  公开号：US20070054951A1

  公开（公告）日：2007-03-08

  Novel cycloalkanoindole derivatives of formula (I) are antagonists of prostaglandins, and as such are useful for the treatment of prostaglandin mediated diseases.

  公式（I）的新型环烷基吲哚衍生物是前列腺素拮抗剂，因此对于治疗前列腺素介导的疾病非常有用。
• FLUORO-METHANESULFONYL-SUBSTITUTED CYCLOALKANOINDOLES AND THEIR USE AS PROSTAGLANDIN D2 ANTAGONISTS
  申请人：Merck Frosst Canada Ltd.

  公开号：EP1631547A1

  公开（公告）日：2006-03-08