4(S)-(1,3-dihydro-1,3-dioxo-2H-isoindol-2-yl)-1,3,4,5-tetrahydro-7-benzyl-8-hydroxy-3-oxo-2H-benzazepin-2-acetic acid

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯氮卓类
• 英文名称: 4(S)-(1,3-dihydro-1,3-dioxo-2H-isoindol-2-yl)-1,3,4,5-tetrahydro-7-benzyl-8-hydroxy-3-oxo-2H-benzazepin-2-acetic acid
• 英文别名: 2-[(4S)-7-benzyl-4-(1,3-dioxoisoindol-2-yl)-8-hydroxy-3-oxo-4,5-dihydro-1H-2-benzazepin-2-yl]acetic acid
• 化学式: C₂₇H₂₂N₂O₆
• 分子量: 470.481
• InChiKey: AEYWBRMMBYSLFY-QFIPXVFZSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  35
• 可旋转键数：
  5
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.19
• 拓扑面积：
  115
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  3-[2(S)-(1,3-dihydro-1,3-dioxo-2H-isoindol-2-yl)-3-(4-benzyloxyphenyl)propanoyl]-1,3-oxazolidin-5-one 在 四氯化锡 作用下， 以 二氯甲烷 为溶剂， 反应 4.0h， 以50%的产率得到4(S)-(1,3-dihydro-1,3-dioxo-2H-isoindol-2-yl)-1,3,4,5-tetrahydro-80hydroxy-3-oxo-2Hbenzazepin-2-acetic acid
  参考文献：
  名称：

  Efficient Synthesis of (S)-4-Phthalimido-1,3,4,5- tetrahydro-8-(2,6-dichlorobenzyloxy)-3-oxo-2H-2-benzazepin-2-acetic Acid (Pht-Hba(2,6-Cl₂-Bn)-Gly-OH)¹

  摘要：

  4-Amino-2-benzazepin-3-ones have proven very useful for studying the biologically active conformations of peptides. The synthesis of Pht-Aba-Xaa-OH by reaction of the corresponding 1,3-oxazolidin-5-one with trifluoromethanesulfonic acid (TFMSA) has been reported in the literature. However, when this procedure was applied to the preparation of Pht-Hba(Bn)-Gly-OH 8, many byproducts were formed and the yield of the desired aminobenzazepinones 7 and 8 was very low. We report in this paper an efficient methodology for the synthesis of Pht-Hba(2,6-Cl-2-Bn)-Gly-OH 17 starting from the commercially available tyro sine. In our procedure, the dipeptide Pht-Tyr(2,6-Cl-2-Bn)-Gly-OH 15 is converted,to the 1,3-oxazolidin-5-one 16 Which then undergoes Friedel-Crafts cyclization in the presence of tin tetrachloride to afford the desired 4-phthalimido-1,3,4,5-tetrahydro-8-(2,6-dichlorobenzyloxy)-2-benzazepin-3-one 17 in excellent yield.

  DOI：

  10.1021/jo000530d

文献信息

• Efficient Synthesis of (<i>S</i>)-4-Phthalimido-1,3,4,5- tetrahydro-8-(2,6-dichlorobenzyloxy)-3-oxo-2<i>H</i>-2-benzazepin-2-acetic Acid (Pht-Hba(2,6-Cl₂-Bn)-Gly-OH)¹
  作者：J. Richard Casimir、Dirk Tourwé、Koen Iterbeke、Gilles Guichard、Jean-Paul Briand

  DOI：10.1021/jo000530d

  日期：2000.10.1

  4-Amino-2-benzazepin-3-ones have proven very useful for studying the biologically active conformations of peptides. The synthesis of Pht-Aba-Xaa-OH by reaction of the corresponding 1,3-oxazolidin-5-one with trifluoromethanesulfonic acid (TFMSA) has been reported in the literature. However, when this procedure was applied to the preparation of Pht-Hba(Bn)-Gly-OH 8, many byproducts were formed and the yield of the desired aminobenzazepinones 7 and 8 was very low. We report in this paper an efficient methodology for the synthesis of Pht-Hba(2,6-Cl-2-Bn)-Gly-OH 17 starting from the commercially available tyro sine. In our procedure, the dipeptide Pht-Tyr(2,6-Cl-2-Bn)-Gly-OH 15 is converted,to the 1,3-oxazolidin-5-one 16 Which then undergoes Friedel-Crafts cyclization in the presence of tin tetrachloride to afford the desired 4-phthalimido-1,3,4,5-tetrahydro-8-(2,6-dichlorobenzyloxy)-2-benzazepin-3-one 17 in excellent yield.