methyl 2-acetamido-3-(4-bromo-1H-indol-3-yl)propanoate | 343846-43-5

• 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: methyl 2-acetamido-3-(4-bromo-1H-indol-3-yl)propanoate
• 英文别名: N-acetyl-4-bromo-DL-tryptophan methyl ester；dl-N-acetyl-4-bromotryptophan methyl ester
• CAS: 343846-43-5
• 化学式: C₁₄H₁₅BrN₂O₃
• 分子量: 339.189
• InChiKey: PLBOHIQKQNTUEJ-UHFFFAOYSA-N

物化性质

• 熔点：
  197-198 °C(Solv: ethyl acetate (141-78-6); hexane (110-54-3))
• 沸点：
  555.3±50.0 °C(Predicted)
• 密度：
  1.496±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.3
• 重原子数：
  20
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  71.2
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  methyl 2-acetamido-3-(4-bromo-1H-indol-3-yl)propanoate 在 盐酸 、 锂硼氢 、 camphor-10-sulfonic acid 、 chloro (2-dicyclohexylphosphino-2 ‘,4’,6’-triisopropyl-1,1’-biphenyl)[2-(2’-amino-1,1‘-biphenyl)]palladium(II) 、 1-羟基苯并三唑 、 O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate 、 N,N-二异丙基乙胺 、 三氟乙酸 、 sodium t-butanolate 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 甲醇 、 二氯甲烷 、 水 、 异丙醇 、 甲苯 为溶剂， 反应 22.0h， 生成 (3R,9S)-6,6-dimethyl-9-propan-2-yl-5-oxa-7,10,16-triazatetracyclo[9.6.1.03,7.015,18]octadeca-1(17),11,13,15(18)-tetraen-8-one
  参考文献：
  名称：

  分子内Buchwald-Hartwig C-N偶联环化反应合成（-）-Epi-Indolactam V

  摘要：

  描述了使用钯和铜催化的分子内N-芳基化策略从简单的可商购起始原料中简明合成（-）-吲哚内酰胺V的合成步骤，该合成过程详细阐述了必要的九元内酰胺环。 。沿线性前体引入诱导结构的元素对实现杂环化步骤以及获得正确的区域选择性和化学选择性至关重要。C-N偶联环化反应中的立体选择性本质是根据钯-酰胺基络合物形成的过渡态上的烯丙基应变最小化来解释的。同时，已经完成了（-）-表-吲哚内酰胺V及其对映异构体的合成。

  DOI：

  10.1021/jo4013767
• 作为产物：
  描述：

  4-溴吲哚 在 乙酸酐 、 溶剂黄146 作用下， 以 甲醇 、 乙酸乙酯 、 甲苯 为溶剂， 反应 4.0h， 生成 methyl 2-acetamido-3-(4-bromo-1H-indol-3-yl)propanoate
  参考文献：
  名称：

  Synthesis and biological evaluation of novel tryptoline derivatives as indoleamine 2,3-dioxygenase (IDO) inhibitors

  摘要：

  Indoleamine 2,3-dioxygenase (IDO) plays a significant role in several disorders such as Alzheimer's disease, age-related cataracts and tumors. A series of novel tryptoline derivatives were synthesized and evaluated for their inhibitory activity against IDO. Substituted tryptoline derivatives (11a, 11c, 11e, 12b and 12c) were demonstrated to be more potent than known inhibitor MTH-Trp. Suzuki-Miyaura cross-coupling reaction of 11a-d with phenylboronic acid proceeded in high yields. In most cases, C5 and C6 substitutions on the corresponding indole ring were well tolerated. The tryptoline derivative 11c is a promising chemical lead for the discovery of novel IDO inhibitors. (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2012.12.028

文献信息

• Total Synthesis without Protection: Three-Step Synthesis of Optically Active Clavicipitic Acids by a Biomimetic Route
  作者：Yuusaku Yokoyama、Hidemasa Hikawa、Masaharu Mitsuhashi、Aki Uyama、Yasuhiro Hiroki、Yasuoki Murakami

  DOI：10.1002/ejoc.200300603

  日期：2004.3

  A three-step synthesis of a mixture of optically active cis- and trans-clavicipitic acids 6, which are ergot alkaloids, was achieved, starting from 4-bromoindole (7) and dl-serine (dl-2). This short synthesis was made possible by omitting the protection and deprotection steps from the synthetic route. The key step was the spontaneous cyclization of 4-vinyltryptophan (10) formed from the Heck reaction

  从 4-溴吲哚 (7) 和 dl-丝氨酸 (dl-2) 开始，实现了光学活性顺式和反式克拉维酸 6（麦角生物碱）混合物的三步合成。通过省略合成路线中的保护和脱保护步骤，使这种短合成成为可能。关键步骤是在水性介质中 4-溴色氨酸 (8) 与 2-甲基-3-丁烯-2-醇 (9) 的 Heck 反应形成的 4-乙烯基色氨酸 (10) 的自发环化。在这项调查中，我们还发现钯催化的 8 与 9 反应显示出有趣的 pH 依赖性；在强碱性条件下，发生 Heck 反应生成 C4-乙烯基化产物 10，而在中性或弱碱性条件下生成 N-烯丙基化产物 19b。(© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004)
• An Efficient Method of Synthesizing Optically Pure N-Boc-4-bromo-N-methyl-1-tosyl-D-tryptophan Methyl Ester, a Key Intermediate in the Synthesis of Optically Active Ergot Alkaloids
  作者：Yuusaku Yokoyama、Kumi Osanai、Masaharu Mitsuhashi、Kazuhiro Kondo、Yasuoki Murakami

  DOI：10.3987/com-00-9137

  日期：——

  Optically pure N-Boc-4-bromo-N-methyl-1-tosyl-D-tryptophan methyl ester (D-4), a key intermediate in the synthesis of optically active ergot alkaloids such as chanoclavine-I (7) and costaclavine (8), was prepared from N-acetyl-4-bromo-D-tryptophan (D-ll) obtained from 4-bromoindole (9) and DL-serine (10) in two steps.
• Synthesis and biological evaluation of novel tryptoline derivatives as indoleamine 2,3-dioxygenase (IDO) inhibitors
  作者：Minoru Tanaka、Xin Li、Hidemasa Hikawa、Takafumi Suzuki、Katsuhiko Tsutsumi、Masashi Sato、Osamu Takikawa、Hideharu Suzuki、Yuusaku Yokoyama

  DOI：10.1016/j.bmc.2012.12.028

  日期：2013.3

  Indoleamine 2,3-dioxygenase (IDO) plays a significant role in several disorders such as Alzheimer's disease, age-related cataracts and tumors. A series of novel tryptoline derivatives were synthesized and evaluated for their inhibitory activity against IDO. Substituted tryptoline derivatives (11a, 11c, 11e, 12b and 12c) were demonstrated to be more potent than known inhibitor MTH-Trp. Suzuki-Miyaura cross-coupling reaction of 11a-d with phenylboronic acid proceeded in high yields. In most cases, C5 and C6 substitutions on the corresponding indole ring were well tolerated. The tryptoline derivative 11c is a promising chemical lead for the discovery of novel IDO inhibitors. (C) 2013 Elsevier Ltd. All rights reserved.
• Synthesis of (−)-Epi-Indolactam V by an Intramolecular Buchwald–Hartwig C–N Coupling Cyclization Reaction
  作者：Michele Mari、Francesca Bartoccini、Giovanni Piersanti

  DOI：10.1021/jo4013767

  日期：2013.8.2

  The synthetic efforts toward the concise synthesis of (−)-indolactam V from simple and commercially available starting materials using palladium- and copper-catalyzed intramolecular N-arylation strategy for the elaboration of the requisite nine-membered lactam ring as the key step are described. The incorporation of a turn-inducing structural element along the linear precursor was fundamental to achieve

  描述了使用钯和铜催化的分子内N-芳基化策略从简单的可商购起始原料中简明合成（-）-吲哚内酰胺V的合成步骤，该合成过程详细阐述了必要的九元内酰胺环。 。沿线性前体引入诱导结构的元素对实现杂环化步骤以及获得正确的区域选择性和化学选择性至关重要。C-N偶联环化反应中的立体选择性本质是根据钯-酰胺基络合物形成的过渡态上的烯丙基应变最小化来解释的。同时，已经完成了（-）-表-吲哚内酰胺V及其对映异构体的合成。