2-甲基-3-(4’-甲氧基苯甲酰基)吲哚 | 26211-90-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吲哚及其衍生物
• 中文名称: 2-甲基-3-(4’-甲氧基苯甲酰基)吲哚
• 中文别名: (4-甲氧基苯基)-(2-甲基-1H-吲哚-3-基)-甲酮；2-甲基-3-(4'-甲氧基苯甲酰基)吲哚
• 英文名称: (4-methoxyphenyl)(2-methyl-1H-indol-3-yl)methanone
• 英文别名: 2-methyl-3-(4-methoxybenzoyl)indole；(4-methoxyphenyl)-(2-methyl-1H-indol-3-yl)methanone
• CAS: 26211-90-5
• 化学式: C₁₇H₁₅NO₂
• 分子量: 265.312
• InChiKey: QZVJIIKWCINHPD-UHFFFAOYSA-N

物化性质

• 熔点：
  214-216 °C
• 沸点：
  445.9±35.0 °C(Predicted)
• 密度：
  1.204±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.8
• 重原子数：
  20
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.12
• 拓扑面积：
  42.1
• 氢给体数：
  1
• 氢受体数：
  2

安全信息

• 海关编码：
  2933990090

反应信息

• 作为反应物：
  描述：

  2-甲基-3-(4’-甲氧基苯甲酰基)吲哚 在 正丁基锂 作用下， 以 四氢呋喃 、 正己烷 为溶剂， 反应 99.0h， 生成 <2-methyl-1-<2-<<(4-methylphenyl)sulfonyl>oxy>ethyl>-1H-indol-3-yl>(4-methoxyphenyl)methanone
  参考文献：
  名称：

  Antinociceptive (aminoalkyl)indoles

  摘要：

  The (aminoalkyl)indole (AAI) derivative pravadoline (1a) inhibited prostaglandin (PG) synthesis in mouse brain microsomes in vitro and ex vivo and exhibited antinociceptive activity in several rodent assays. In vitro structure-activity relationship studies of this new class of PG synthesis inhibitors revealed a correspondence in three respects to those reported for the arylacetic acids: (1) ''alpha-methylation'' caused an increase in PG inhibitory potency, (2) the (R)-alpha-methyl isomer was more active than the S isomer, (3) the hypothesized aroyl group conformation of the 2-methyl derivatives corresponded to the proposed and reported ''active'' conformations of the aroyl and related aromatic acetic acid derivatives. The H-1 NMR chemical shift of the C-4 hydrogen of pravadoline in comparison to the deshielding seen with 50, which lacks a substituent at C-2, suggested that the carbonyl group of pravadoline is located near C-2 but is located near C-4 in 50. Associated with this conformational change of the carbonyl group of 1a is a diminution of PG synthetase inhibitory activity. The results of UV and difference nuclear Overhauser studies of the two compounds were consistent with these conformational assignments. The low eudismic ratios of the alpha-methyl derivatives and the observation that the side chain may be extended by three methylene groups without significant loss of PG inhibitory potency suggests that this class of inhibitors bound less strongly and less selectively to the active site of PG synthetase than do the arylacetic acids. Two AAIs, 1a and 30, were found to be metabolized to the corresponding acetic acid derivatives, both of which inhibited PG synthesis. An exception to the observation that the antinociceptive activity of the AAIs was associated with PG synthetase inhibitory activity was the 1-naphthoyl derivative 67 since neither it nor its acetic acid metabolite 74 inhibited PG synthesis. Yet 67 was antinociceptive in four different rodent assays. This naphthoyl derivative, like opioids, also inhibited electrically stimulated contractions in the mouse vas deferens (MVD) preparation. Unlike opioids, however, the inhibition was not antagonized by naloxone. A subseries of AAIs was identified, of which 67 was prototypic. These compounds lacked PG synthetase inhibitory activity, but their inhibitory potency in MVD preparations correlated roughly with their antinociceptive potency in vivo. Pravadoline was also inhibitory in the MVD. Its antinociceptive activity, therefore, may be a consequence of both its PG synthetase inhibitory potency and another antinociceptive mechanism, the latter associated with its inhibitory potency in the MVD. The evidence is summarized which suggests that this second antinociceptive mechanism is associated with binding to the recently characterized cannabinoid receptor.

  DOI：

  10.1021/jm00107a034
• 作为产物：
  描述：

  2,2,2-trifluoro-N-(2-iodophenyl)acetamide 在 bis-triphenylphosphine-palladium(II) chloride 、 四(三苯基膦)钯 copper(l) iodide 、 一氧化碳 、 potassium carbonate 、 二乙胺 作用下， 以 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 25.0~45.0 ℃ 、405.3 kPa 条件下， 反应 7.0h， 生成 2-甲基-3-(4’-甲氧基苯甲酰基)吲哚
  参考文献：
  名称：

  通过钯催化的2-炔基三氟乙酰苯胺与芳基卤化物和乙烯基三氟甲磺酸酯的2-催化取代的3-acylindoles

  摘要：

  在碳酸钾的存在下，在一氧化碳气氛（1或7 atm）下，钯易于催化的2-炔基三氟乙酰苯胺与芳基化物和乙烯基三氟甲磺酸酯的反应，可公平地以良好的收率产生s 2-取代的3-酰基吲哚。事实证明，氮氢键的酸度对于反应的成功至关重要。该方法已被用于合成普鲁瓦多林，该药物对人的术后疼痛具有镇痛作用。

  DOI：

  10.1016/s0040-4020(01)80766-3

文献信息

• Direct Synthesis of 3-Acylindoles through Rhodium(III)-Catalyzed Annulation of<i>N</i>-Phenylamidines with α-Cl Ketones
  作者：Jianhui Zhou、Jian Li、Yazhou Li、Chenglin Wu、Guoxue He、Qiaolan Yang、Yu Zhou、Hong Liu

  DOI：10.1021/acs.orglett.8b03383

  日期：2018.12.7

  versatile 3-acylindoles through Rh(III)-catalyzed C–H activation and annulation cascade of N-phenylamidines with α-Cl ketones was developed, in which α-Cl ketones serve as unusual one-carbon (sp3) synthons. This strategy features high regioselectivity, efficiency, wide substrate tolerance, and mild reaction conditions, which further underscore its synthetic utility in drug molecule synthesis.

  在本研究中，开发了一种新的合成策略，可通过Rh（III）催化的C–H活化和N-苯基am与α-Cl酮的环合级联反应直接生产通用的3-acylindoles ，其中α-Cl酮用作不寻常的一碳（sp 3）合成子。该策略具有较高的区域选择性，效率，宽的底物耐受性和温和的反应条件，这进一步强调了其在药物分子合成中的合成效用。
• Transfer of activation from indoles to alcohols: A new method for the synthesis of aminoethylindoles
  作者：Michael A. Eissenstat、John D. Weaver

  DOI：10.1016/0040-4039(95)00229-6

  日期：1995.3

  Transfer of a sulfonyl group from an indole nitrogen to a β-amino alkoxide generates an indole anion and an aminoethylsulfonate which react to give aminoethylindoles.

  磺酰基从吲哚氮到β-氨基醇盐的转移产生吲哚阴离子和氨基乙基磺酸盐，它们反应生成氨基乙基吲哚。
• 高价碘试剂介导制备吲哚衍生物的应用
  申请人：南开大学

  公开号：CN108752257B

  公开（公告）日：2021-05-11

  本发明涉及一种高价碘试剂介导制备吲哚衍生物的应用，具体是有机三价碘试剂氨基磺酸亚碘酰苯在制备N‑保护2‑取代吲哚类化合物及吲哚美辛(Indometacin)、齐多美辛(zidometacin)、普拉多林（pravadoline）的应用。本发明涉及的有机三价碘试剂氨基磺酸亚碘酰苯在制备N‑保护2‑取代吲哚类化合物的应用中，反应经历了底物的官能团互换。此外，在该应用中氨基磺酸亚碘酰苯扮演了两个重要的角色，即既做氧化剂又做Brønsted酸。该应用具有区域选择性好、底物范围广、条件温和、操作简单、实验步骤可放大等优点。本发明提供的有机三价碘试剂氨基磺酸亚碘酰苯在制备吲哚美辛、齐多美辛及普拉多林的应用具有合成效率高、操作简单等优点。
• Palladium‐catalyzed cyclization reaction of N‐(2‐Haloaryl)alkynylimines: Synthesis of 3‐acylindoles using water as the sole solvent and oxygen source
  作者：An‐An Zhang、Tuanjie Meng、Wenli Wang、Xueli Liu、Yupei Zhu、Lantao Liu

  DOI：10.1002/aoc.5513

  日期：2020.4

  efficient strategy for the preparation of 3‐acylindoles via palladium‐catalyzed cyclization reaction of N‐(2‐haloaryl)alkynylimines in water has been developed. The reaction tolerates a wide range of functional groups, and the corresponding 3‐acylindoles were obtained in high yields using water as the sole solvent and oxygen sources. Additionally, this method could provide a short synthesis route for

  已开发出一种简单有效的策略，可通过钯催化水中N-（2-卤代芳基）炔基limines的环化反应制备3-acylindoles 。该反应可耐受各种官能团，并且使用水作为唯一的溶剂和氧气源，可以高收率获得相应的3-acylindoldols。此外，该方法可以为II期镇痛药Pravadoline提供短的合成途径。
• Cyclooctatetraene: A Bioactive Cubane Paradigm Complement
  作者：Hui Xing、Sevan D. Houston、Xuejie Chen、Sussan Ghassabian、Tyler Fahrenhorst‐Jones、Andy Kuo、Cody‐Ellen P. Murray、Kyna‐Anne Conn、Kara N. Jaeschke、Da‐Yun Jin、Cielo Pasay、Paul V. Bernhardt、Jed M. Burns、John Tsanaktsidis、G. Paul Savage、Glen M. Boyle、James J. De Voss、James McCarthy、Gimme H. Walter、Thomas H. J. Burne、Maree T. Smith、Jian‐Ke Tie、Craig M. Williams

  DOI：10.1002/chem.201806277

  日期：2019.2.21

  carbocyclic systems lack π character, which is often critical for mediating key biological interactions. This electronic property restriction associated with cubane has been addressed herein with cyclooctatetraene (COT), using known pharmaceutical and agrochemical compounds as templates. COT either outperformed or matched cubane in multiple cases suggesting that versatile complementarity exists between

  古巴烷最近被验证为苯环（生物）等排体，但高度紧张的笼式碳环系统缺乏 π 特征，而这对于介导关键的生物相互作用通常至关重要。本文已使用已知的药物和农业化学化合物作为模板，用环辛四烯(COT)解决了与立方烷相关的电子特性限制。在多种情况下，COT 的性能优于或与立方烷相匹配，这表明两个系统之间存在多功能互补性，可增强生物活性分子的发现。