2-(1H-吲哚-3-基甲基)苯甲酸 | 1221-99-4

• 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
• 中文名称: 2-(1H-吲哚-3-基甲基)苯甲酸
• 英文名称: 3-(o-Carboxy-benzyl)-indol
• 英文别名: 2-(1h-Indol-3-ylmethyl)benzoic acid
• CAS: 1221-99-4
• 化学式: C₁₆H₁₃NO₂
• 分子量: 251.285
• InChiKey: UKOWEQHFZIOAJN-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  19
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.06
• 拓扑面积：
  53.1
• 氢给体数：
  2
• 氢受体数：
  2

文献信息

• [EN] PROCESS FOR THE PREPARATION OF ZAFIRLUKAST<br/>[FR] PROCEDE RELATIF A L'ELABORATION DE ZAFIRLUKAST
  申请人：ISP FINETECH LTD

  公开号：WO2002046153A2

  公开（公告）日：2002-06-13

  The present invention provides a novel process for the preparation of alkyl (1-alkylindol-3-ylmethyl)benzoate derivatives which process comprises the steps of: (a) reacting of an alkyl (halomethyl)benzoate with excess of an indole, said indole being unsubstituted at positions 1-, 2- and 3-, under conditions promoting alkylation at the 3-position of the indole to yield a mixture comprising alkyl (indol-3-ylmethyl)benzoate and unreacted starting indole,(b) treating the mixture obtained in step (a) with base to yield a mixture, comprising the salt of (indol-3-ylmethyl)benzoic acid and the unreacted indole, (c) recovering the unreacted indole from the mixture obtained in step (b), and recycling the indole as starting material to step (a), (d) isolating the salt of (indol-3-ylmethyl)benzoic acid and/or acidifying the salt to form (indol-3-ylmethyl)benzoic acid, (e) reacting the (indol-3-ylmethyl)benzoic acid or its salt with alkylating agent in the presence of base to form the desired alkyl (1-alkylindol-3-ylmethyl)benzoate. The above process affords also the preparation of the anti-asthmatic leukotriene antagonist zafirlukast. In such case, methyl 3-methoxy-4-(1-methyl-5-nitroindol-3-ylmethyl)benzoate [1a] is formed in step (e) of the process and this compound is subsequently converted into zafirlukast by known methods.

  本发明提供了一种制备烷基（1-烷基吲哚-3-基甲基）苯甲酸酯衍生物的新方法，该方法包括以下步骤：（a）反应烷基（卤甲基）苯甲酸酯和过量的吲哚，在促进吲哚3位烷基化的条件下生成包含烷基（吲哚-3-基甲基）苯甲酸酯和未反应的起始吲哚的混合物，（b）用碱处理步骤（a）中获得的混合物，生成包含（吲哚-3-基甲基）苯甲酸盐和未反应的吲哚的混合物，（c）从步骤（b）中获得的混合物中回收未反应的吲哚，并将吲哚作为起始材料回收到步骤（a），（d）分离（吲哚-3-基甲基）苯甲酸盐和/或使盐酸化形成（吲哚-3-基甲基）苯甲酸，（e）在碱存在下，将（吲哚-3-基甲基）苯甲酸或其盐与烷基化试剂反应，形成所需的烷基（1-烷基吲哚-3-基甲基）苯甲酸酯。上述方法还可用于制备抗哮喘的白三烯受体拮抗剂扎菲鲁卡斯特。在这种情况下，步骤（e）中形成甲基3-甲氧基-4-（1-甲基-5-硝基吲哚-3-基甲基）苯甲酸酯[1a]，随后通过已知方法将该化合物转化为扎菲鲁卡斯特。
• Process for the preparation of zafirlukast
  申请人：——

  公开号：US20040186300A1

  公开（公告）日：2004-09-23

  The present invention provides a novel process for the preparation of alkyl (1-alkylindol-3-ylmethyl)benzoate derivatives which process comprises the steps of: (a) reacting of an alkyl (halomethyl)benzoate with excess of an indole, said indole being unsubstituted at positions 1-, 2- and 3-, under conditions promoting alkylation at the 3-position of the indole to yield a mixture comprising alkyl (indol-3-ylmethyl)benzoate and unreacted starting indole, (b) treating the mixture obtained in step (a) with base to yield a mixture, comprising the salt of (indol-3-ylmethyl)benzoic acid and the unreacted indole, (c) recovering the unreacted indole from the mixture obtained in step (b), and recycling the indole as starting material to step (a), (d) isolating the salt of (indol-3-ylmethyl)benzoic acid and/or acidifying the salt to form (indol-3-ylmethyl)benzoic acid, (e) reacting the (indol-3-ylmethyl)benzoic acid or it's salt with alkylating agent in the presence of base to form the desired alkyl (1-alkylindol-3-ylmethyl)benzoate. The above process affords also the preparation of the anti-asthmatic leukotriene antagonist zafirlukast. In such case, methyl 3-methoxy-4-(1-methyl-5-nitroindol-3-ylmethyl)benzoate [a]is formed in step (e) of the process and this compound is subsequently converted into zafirlukast by known methods.

  本发明提供了一种新型的制备烷基（1-烷基吲哚-3-基甲基）苯甲酸酯衍生物的方法，该方法包括以下步骤：（a）反应烷基（卤甲基）苯甲酸酯与过量的吲哚，在促进吲哚3位烷基化的条件下，生成包含烷基（吲哚-3-基甲基）苯甲酸酯和未反应的起始吲哚的混合物；（b）用碱处理步骤（a）中得到的混合物，生成包含（吲哚-3-基甲基）苯甲酸盐和未反应的吲哚的混合物；（c）从步骤（b）中得到的混合物中回收未反应的吲哚，并将吲哚作为起始材料回收到步骤（a）中；（d）分离（吲哚-3-基甲基）苯甲酸盐和/或使盐酸化形成（吲哚-3-基甲基）苯甲酸；（e）在碱的存在下，将（吲哚-3-基甲基）苯甲酸或其盐与烷基化试剂反应，形成所需的烷基（1-烷基吲哚-3-基甲基）苯甲酸酯。上述方法还可用于制备抗哮喘的白三烯受体拮抗剂扎菲鲁卡斯特。在这种情况下，步骤（e）中形成甲基3-甲氧基-4-（1-甲基-5-硝基吲哚-3-基甲基）苯甲酸酯，并随后通过已知方法将该化合物转化为扎菲鲁卡斯特。