methyl 2-(4-methylphenylsulfonamido)-3-(1H-indol-3-yl)propanoate | 79659-73-7

• 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-(4-methylphenylsulfonamido)-3-(1H-indol-3-yl)propanoate
• 英文别名: Tos-Trp-OMe；methyl N-[(4-methylphenyl)sulfonyl]tryptophanate；methyl 3-(1H-indol-3-yl)-2-[(4-methylphenyl)sulfonylamino]propanoate
• CAS: 79659-73-7
• 化学式: C₁₉H₂₀N₂O₄S
• 分子量: 372.445
• InChiKey: UHSKSBWQSHLITK-UHFFFAOYSA-N

物化性质

• 熔点：
  126-127 °C(Solv: ethyl acetate (141-78-6))
• 沸点：
  592.5±60.0 °C(Predicted)
• 密度：
  1.316±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  26
• 可旋转键数：
  7
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.21
• 拓扑面积：
  96.6
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  methyl 2-(4-methylphenylsulfonamido)-3-(1H-indol-3-yl)propanoate 在 potassium phosphate 、 水 、 1,4-diaza-bicyclo[2.2.2]octane 、 lithium chloride 、 copper(I) bromide 、 N,N'-二甲基乙二胺 、 10-甲基-9-均三甲苯基吖啶高氯酸盐 作用下， 以 二氯甲烷 、 甲苯 为溶剂， 反应 54.0h， 生成 methyl (2S)-4-phenyl-3-tosyl-2,3,5a,6-tetrahydro-1H-pyrrolo[3',2':3,4]thieno[2,3-b]indole-2-carboxylate-5,5-dioxide
  参考文献：
  名称：

  可见光诱导[2+2+1]脱芳构级联环化吲哚/呋喃炔烃合成磺酰基多环化合物

  摘要：

  在此，我们报道了可见光诱导的吲哚/呋喃炔烃与 NaHSO 3的 [2+2+1] 脱芳族级联环化，提供了一系列不同的高应变磺酰基多环化合物。与我们之前的工作相比，该方法不需要使用额外的牺牲氧化剂，反应范围更广。初步机理研究表明，吲哚部分引发了反应，该反应通过单电子氧化途径进行。分子内加成捕获SO 2形成的烯基自由基, 并将所得物质环化以提供最终产品。此外，DFT 计算表明，吲哚环或侧链上的基团可能影响 IM-RC-I 反应位点的单电子分布，该分布可能是螺环化的决定性因素。

  DOI：

  10.1002/adsc.202200331
• 作为产物：
  描述：

  DL-色氨酸 在 氯化亚砜 、 三乙胺 作用下， 以 甲醇 、 二氯甲烷 为溶剂， 生成 methyl 2-(4-methylphenylsulfonamido)-3-(1H-indol-3-yl)propanoate
  参考文献：
  名称：

  Design and bio-evaluation of indole derivatives as potent Kv1.5 inhibitors

  摘要：

  Atrial fibrillation (AF) is one of the common arrhythmias that threaten human health. Kv1.5 potassium channel is reported as an efficacious and safe target for the treatment of AF. In this paper, we designed and synthesized three series of compounds through modifying the lead compound RH01617 that was screened out by the pharmacophore model we reported earlier. All of the compounds were evaluated by the whole-patch lamp technology and most of them possessed potent inhibitory activities against Kv1.5. Compounds IIIi and IIIl were evaluated for the target selectivity as well as the pharmacodynamic effects in an isolated rat model. Due to the promising pharmacological behavior, compound IIIl deserves further pharmacodynamic and pharmacokinetic evaluations. (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2013.08.041

文献信息

• Replacing halogenated solvents by a butyl acetate solution of bisphenol S in the transformations of indoles
  作者：Feng Gao、Francesco Ferlin、Rongxian Bai、Minghao Li、Luigi Vaccaro、Yanlong Gu

  DOI：10.1039/d1gc00778e

  日期：——

  A butyl acetate solution of bisphenol S (BPS) was proved to be able to replace hazardous halogenated solvents in the transformation of indoles. Measurement with Kamlet–Taft solvatochromic parameters disclosed that the polarity of the BPS-containing butyl acetate was enhanced greatly. The protocol not only conferred a convenient way to minimize the use of halogenated solvents in the synthesis of indole

  事实证明，双酚S（BPS）的乙酸丁酯溶液可以代替吲哚转化中的危险卤代溶剂。用Kamlet-Taft溶剂化变色参数进行的测量表明，含BPS的乙酸丁酯的极性大大增强了。该方案不仅为在吲哚衍生物的合成中减少卤化溶剂的使用提供了便利的方法，而且还使乙酸丁酯溶剂和BPS添加剂都能成功回收，从而增强了反应系统的绿色度。
• A general method for the synthesis of indoles bearing a variety of substituents at the β-position, and its application to the synthesis of l-tryptophan
  作者：Tatsuya Shono、Yoshihiro Matsumura、Takenobu Kanazawa

  DOI：10.1016/s0040-4039(00)81629-9

  日期：1983.1

  A general synthetic method of β-substituted indoles such as indoleacetic acid, tryptamine and L-tryptophan has been exploited utilizing α-methoxylated amides, lactams, a carbamate, and sulfonamides, easily obtainable by an electrochemical method, as key intermediates.

  已经利用α-甲氧基化酰胺，内酰胺，氨基甲酸酯和磺酰胺作为关键中间体，开发了β-取代的吲哚如吲哚乙酸，色胺和L-色氨酸的一般合成方法。
• Mild Reductive Cleavage of Tryptophan and Histidine Side-Chain Protecting Groups
  作者：Hernani L. S. Maia、Luís S. Monteiro、Joana Sebastião

  DOI：10.1002/1099-0690(200105)2001:10<1967::aid-ejoc1967>3.0.co;2-x

  日期：2001.5

  The activation potentials of the p-toluenesulfonyl and benzoyl groups as determined by cyclic voltammetry when they are linked to indole or imidazole are less negative than when these groups are linked to aliphatic amines. This makes them most suitable for side-chain protection of tryptophan and histidine, as it allows mild selective cleavage not only by controlled-potential electrolysis but also by

  当对甲苯磺酰基和苯甲酰基与吲哚或咪唑相连时，通过循环伏安法测定的对甲苯磺酰基和苯甲酰基的活化电位比这些基团与脂肪胺相连时的负性小。这使它们最适合色氨酸和组氨酸的侧链保护，因为它不仅可以通过控制电位电解而且可以通过使用无水甲醇中的镁或汞活化的铝进行化学还原来进行温和的选择性裂解。
• Copper‐Catalyzed Chemoselective Divergent Carbene Insertion into the N−H bonds of Tryptamines
  作者：Dharmendra Kumar、Malleswara Rao Kuram

  DOI：10.1002/adsc.202300893

  日期：2023.11.21

  synthesis. Herein, we have developed a chemoselective copper-catalyzed carbene insertion protocol onto N−H bonds of tryptamine derivatives. Divergent insertion products are obtained by varying the nucleophilicity of the aliphatic NH of tryptamine with electron-donating or electron-withdrawing groups. The reaction provided N−H insertion products with broad substrate scope in good yields.

  轻松获得具有化学选择性的不同产物在有机合成中非常重要。在此，我们开发了一种化学选择性铜催化卡宾插入色胺衍生物 N−H 键的方案。通过改变色胺的脂肪族NH与给电子或吸电子基团的亲核性来获得不同的插入产物。该反应以良好的产率提供了具有广泛底物范围的 NH 插入产物。
• Ca(II)-Catalyzed Cascade Reaction of Tryptamines with Propargylic Alcohols: Temperature-Driven Ring Opening and Closing via the Allene Migration Pathway for the Synthesis of Pyrrolo[1,2-<i>a</i>]indoles
  作者：Ashok Kale、Su Jeong Kwon、Joohan Lee、Jae Kyun Lee、Kyeong Lee

  DOI：10.1021/acs.orglett.3c04357

  日期：2024.2.16

  temperature-dependent cascade of reactions between tryptamines and propargylic alcohols was developed to achieve selective formation of pyrroloindoline and pyrrolo[1,2-a]indole heterocycles by Ca(II) catalysis. The cascade consists of electrophilic addition of allene at the C3 carbon of indole followed by intramolecular cyclization at 60 °C to yield pyrroloindolines. Furthermore, simultaneous 1,2-allene

  开发了色胺和炔丙醇之间的温度依赖性级联反应，以通过 Ca(II) 催化选择性形成吡咯并吲哚啉和吡咯并[1,2- a ]吲哚杂环。该级联包括在吲哚的 C3 碳上进行丙二烯的亲电加成，然后在 60 °C 下进行分子内环化，生成吡咯并吲哚啉。此外，同时进行1,2-丙二烯迁移和吡咯烷开环，然后在回流温度下通过C-N键形成进行分子内环化，以获得吡咯并[1,2- a ]吲哚支架。该方案的优点是底物范围广泛、反应过程干净、可扩展性以及良好至优异的产率。