ethyl 6-methoxy-2-(methoxycarbonyl)-1,2,3,4-tetrahydroisoquinoline-3-carboxylate | 134388-99-1

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: ethyl 6-methoxy-2-(methoxycarbonyl)-1,2,3,4-tetrahydroisoquinoline-3-carboxylate
• 英文别名: 3-O-ethyl 2-O-methyl 6-methoxy-3,4-dihydro-1H-isoquinoline-2,3-dicarboxylate
• CAS: 134388-99-1
• 化学式: C₁₅H₁₉NO₅
• 分子量: 293.32
• InChiKey: PCKLSLTYADVOQJ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.75
• 重原子数：
  21.0
• 可旋转键数：
  3.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.47
• 拓扑面积：
  65.07
• 氢给体数：
  0.0
• 氢受体数：
  5.0

反应信息

• 作为反应物：
  描述：

  ethyl 6-methoxy-2-(methoxycarbonyl)-1,2,3,4-tetrahydroisoquinoline-3-carboxylate 在 sodium hydroxide 作用下， 以 乙醇 为溶剂， 以83%的产率得到6-methoxy-2-(methoxycarbonyl)-1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid
  参考文献：
  名称：

  Syntheses of 6-oxodecahydroisoquinoline-3-carboxylates. Useful intermediates for the preparation of conformationally defined excitatory amino acid antagonists

  摘要：

  We have prepared three of the four possible diastereomers of ethyl 6-oxo-2-(methoxycarbonyl)decahydroisoquinoline-3-carboxylic acid (two cis- ring and one trans ring juncture ketones, 3a-c) by a convergent route from (+/-)-m-tyrosine. These ketones are useful intermediates for the preparation of conformationally constrained acidic amino acids as N-methyl-D-aspartic acid (NMDA) receptor antagonists, e.g., LY274614 and LY233536 (1 and 2, respectively). The cis ring juncture ketones were prepared selectively by hydrogenation of a key tetrahydroisoquinoline intermediate 7, while the corresponding trans ring juncture ketone was prepared selectively by consecutive dissolving metal reductions of the tetrahydroisoquinoline 8. One of the ketones, 3b, that possesses the optimal stereochemical array for NMDA antagonist activity, was resolved via the alpha-methylbenzylamine salts of the corresponding acid to allow for determination of the active optical isomer of these amino acids. The synthesis and resolution of the keto esters can easily be performed on a multigram scale.

  DOI：

  10.1021/jo00014a012
• 作为产物：
  描述：

  1,2,3,4-四氢-6-羟基异喹啉-3-羧酸 在 盐酸 、 potassium carbonate 、 N,N-二异丙基乙胺 作用下， 以 二氯甲烷 、 丙酮 为溶剂， 反应 0.33h， 生成 ethyl 6-methoxy-2-(methoxycarbonyl)-1,2,3,4-tetrahydroisoquinoline-3-carboxylate
  参考文献：
  名称：

  Syntheses of 6-oxodecahydroisoquinoline-3-carboxylates. Useful intermediates for the preparation of conformationally defined excitatory amino acid antagonists

  摘要：

  We have prepared three of the four possible diastereomers of ethyl 6-oxo-2-(methoxycarbonyl)decahydroisoquinoline-3-carboxylic acid (two cis- ring and one trans ring juncture ketones, 3a-c) by a convergent route from (+/-)-m-tyrosine. These ketones are useful intermediates for the preparation of conformationally constrained acidic amino acids as N-methyl-D-aspartic acid (NMDA) receptor antagonists, e.g., LY274614 and LY233536 (1 and 2, respectively). The cis ring juncture ketones were prepared selectively by hydrogenation of a key tetrahydroisoquinoline intermediate 7, while the corresponding trans ring juncture ketone was prepared selectively by consecutive dissolving metal reductions of the tetrahydroisoquinoline 8. One of the ketones, 3b, that possesses the optimal stereochemical array for NMDA antagonist activity, was resolved via the alpha-methylbenzylamine salts of the corresponding acid to allow for determination of the active optical isomer of these amino acids. The synthesis and resolution of the keto esters can easily be performed on a multigram scale.

  DOI：

  10.1021/jo00014a012