(S)-3-((R)-1-Benzoyl-2,3-dihydro-1H-indol-3-yl)-2-(2,2,2-trifluoro-acetylamino)-propionic acid | 133148-95-5

• 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: (S)-3-((R)-1-Benzoyl-2,3-dihydro-1H-indol-3-yl)-2-(2,2,2-trifluoro-acetylamino)-propionic acid
• 英文别名: (2S)-3-[(3R)-1-benzoyl-2,3-dihydroindol-3-yl]-2-[(2,2,2-trifluoroacetyl)amino]propanoic acid
• CAS: 133148-95-5
• 化学式: C₂₀H₁₇F₃N₂O₄
• 分子量: 406.361
• InChiKey: CDCJBMXXBOWOKX-ZFWWWQNUSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  29
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  86.7
• 氢给体数：
  2
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  (S)-3-((R)-1-Benzoyl-2,3-dihydro-1H-indol-3-yl)-2-(2,2,2-trifluoro-acetylamino)-propionic acid 在 palladium on activated charcoal manganese(IV) oxide 、 sodium hydroxide 、 sodium tetrahydroborate 、 正丁基锂 、 三氯化铝 、 草酰氯 、 氢气 、 溴 、 sodium acetate 、 potassium carbonate 、 三氟乙酸酐 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 、 水 、 溶剂黄146 、 N,N-二甲基甲酰胺 、 乙腈 为溶剂， -65.0~200.0 ℃ 、310.27 kPa 条件下， 反应 59.0h， 生成 (4R)-4-(二丙基氨基)-1,3,4,5-四氢苯并[cd]吲哚-6-甲酰胺
  参考文献：
  名称：

  Synthetic Studies toward the Partial Ergot Alkaloid LY228729, a Potent 5HT_1A Receptor Agonist

  摘要：

  Synthetic studies on LY228729 (3) afforded two innovative approaches for the construction of this class of partial ergoline 5HT(1a) receptor agonists. The first synthesis is based upon a diastereoselective epoxidation of racemic olefin 5, followed by ring opening and covalent resolution to furnish the key amino alcohol 8. Aziridination of amino alcohol 8, with subsequent tandem hydrogenolysis of the benzylic aziridine and auxiliary bonds, provided access to the optically active primary amine 13. A novel catalytic carboxamidation reaction installed the requisite side chain, Alternatively, the chiral pool was drawn upon for the single stereogenic center by virtue of L-tryptophan, albeit by a more circuitous route than expected. L-Tryptophan was differentially protected and reduced to the indoline diastereomers 26a,b which were separated by fractional crystallization. The two indoline diastereoisomers were independently cyclized by a Friedel-Crafts protocol, which under thermodynamic control afforded enantiomeric ketones 30a. The ketone was deoxygenated with a two-step reduction protocol to intersect the initial route and complete the second total synthesis. The two routes offer complementary access to this exciting class of partial ergot alkaloids.

  DOI：

  10.1021/jo971256z
• 作为产物：
  描述：

  (S)-3-(1H-indol-3-yl)-2-(2,2,2-trifluoroacetamido)propanoic acid 在 三乙基硅烷 作用下， 生成 (S)-3-((R)-1-Benzoyl-2,3-dihydro-1H-indol-3-yl)-2-(2,2,2-trifluoro-acetylamino)-propionic acid
  参考文献：
  名称：

  由L-色氨酸制备1-苯甲酰基-4-（氨基）-1,2,2a，3,4,5-六氢苯并[ CD ]吲哚

  摘要：

  衍生自L-色氨酸的酸6a已被证明是部分麦角结构（如3）的有用前体。通过分子内的Friedel-Crafts环化和C-5脱氧程序，通过四个步骤，以6a的总收率从4a制备了光学纯胺（+）-13（3的合成关键中间体）。

  DOI：

  10.1016/s0040-4039(00)97304-0

文献信息

• VARIE, DAVID L., TETRAHEDRON LETT., 31,(1990) N2, C. 7583-7586
  作者：VARIE, DAVID L.

  DOI：——

  日期：——
• Synthetic Studies toward the Partial Ergot Alkaloid LY228729, a Potent 5HT_1A Receptor Agonist
  作者：M. A. Carr、P. E. Creviston、D. R. Hutchison、J. H. Kennedy、V. V. Khau、T. J. Kress、M. R. Leanna、J. D. Marshall、M. J. Martinelli、B. C. Peterson、D. L. Varie、J. P. Wepsiec

  DOI：10.1021/jo971256z

  日期：1997.12.1

  Synthetic studies on LY228729 (3) afforded two innovative approaches for the construction of this class of partial ergoline 5HT(1a) receptor agonists. The first synthesis is based upon a diastereoselective epoxidation of racemic olefin 5, followed by ring opening and covalent resolution to furnish the key amino alcohol 8. Aziridination of amino alcohol 8, with subsequent tandem hydrogenolysis of the benzylic aziridine and auxiliary bonds, provided access to the optically active primary amine 13. A novel catalytic carboxamidation reaction installed the requisite side chain, Alternatively, the chiral pool was drawn upon for the single stereogenic center by virtue of L-tryptophan, albeit by a more circuitous route than expected. L-Tryptophan was differentially protected and reduced to the indoline diastereomers 26a,b which were separated by fractional crystallization. The two indoline diastereoisomers were independently cyclized by a Friedel-Crafts protocol, which under thermodynamic control afforded enantiomeric ketones 30a. The ketone was deoxygenated with a two-step reduction protocol to intersect the initial route and complete the second total synthesis. The two routes offer complementary access to this exciting class of partial ergot alkaloids.
• Preparation of 1-benzoyl-4-(amino)-1,2,2a,3,4,5-hexahydrobenz[CD]indoles from L-tryptophan
  作者：David L. Varie

  DOI：10.1016/s0040-4039(00)97304-0

  日期：1990.1

  Acid6a, derived from L-tryptophan, has been shown to be a useful precursor to partial ergot structures such as3. Optically pure amine(+)−13, a key intermediate in the synthesis of3, was prepared in 45% overall yield from6a via a four step sequence employing an intramolecular Friedel-Crafts cyclization and a C-5 deoxygenation procedure.

  衍生自L-色氨酸的酸6a已被证明是部分麦角结构（如3）的有用前体。通过分子内的Friedel-Crafts环化和C-5脱氧程序，通过四个步骤，以6a的总收率从4a制备了光学纯胺（+）-13（3的合成关键中间体）。