1-(6-bromo-1-methyl-1H-indol-3-yl)-2,2,2-trifluoroethan-1-one | 1296202-13-5

• 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
• 英文名称: 1-(6-bromo-1-methyl-1H-indol-3-yl)-2,2,2-trifluoroethan-1-one
• 英文别名: 1-(6-bromo-1-methylindol-3-yl)-2,2,2-trifluoroethanone
• CAS: 1296202-13-5
• 化学式: C₁₁H₇BrF₃NO
• 分子量: 306.082
• InChiKey: DPNIZCAXMMHNOD-UHFFFAOYSA-N

物化性质

• 沸点：
  353.2±37.0 °C(Predicted)
• 密度：
  1?+-.0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.8
• 重原子数：
  17
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.18
• 拓扑面积：
  22
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  1-(6-bromo-1-methyl-1H-indol-3-yl)-2,2,2-trifluoroethan-1-one 在 trans-bis(triphenylphosphine)palladium dichloride 、 sodium carbonate 、 三乙胺 、 Methanaminium,N-[(dimethylamino)(3H-1,2,3-triazolo[4,5-b]pyridin-3-yloxy)methylene]-N-methyl-, hexafluorophosphate(1-) 、 sodium hydroxide 作用下， 以 1,4-二氧六环 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 14.0h， 生成 N-(2-(dimethylamino)ethyl)-N-(3-methoxybenzyl)-1-methyl-6-(1H-pyrazol-4-yl)-1H-indole-3-carboxamide
  参考文献：
  名称：

  Discovery and optimization of indole and 7-azaindoles as Rho kinase (ROCK) inhibitors (Part-II)

  摘要：

  Therapeutic interventions with Rho kinase (ROCK) inhibitors may effectively treat several disorders such as hypertension, stroke, cancer, and glaucoma. Herein we disclose the optimization and biological evaluation of potent novel ROCK inhibitors based on substituted indole and 7-azaindole core scaffolds. Substitutions on the indole C3 position and on the indole NH and/or amide NH positions all yielded potent and selective ROCK inhibitors (25, 42, and 50). Improvement of aqueous solubility and tailoring of in vitro and in vivo DMPK properties could be achieved through these substitutions. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2011.09.084
• 作为产物：
  描述：

  6-溴吲哚 在 caesium carbonate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 生成 1-(6-bromo-1-methyl-1H-indol-3-yl)-2,2,2-trifluoroethan-1-one
  参考文献：
  名称：

  一种简单高效的抗癌吲哚生物碱TMC-205及其类似物的全合成

  摘要：

  通过无保护基团 (PGF) 和氧化还原经济策略，TMC-205 的简明合成分两步完成。在该方法中，使用高产率 Pinnick 氧化和具有高原子经济性以及高区域和立体选择性（E-异构体）的实用 Heck 脱水反应，并进一步应用于其活性类似物的全合成。这条新建立的路线将有利于未来的构效关系（SAR）和生物学研究。本文展示的合成策略和方法可以扩展到相关的生物活性天然产物。

  DOI：

  10.1016/j.tetlet.2021.153137

文献信息

• Salicylaldehyde-Promoted Cobalt-Catalyzed C–H/N–H Annulation of Indolyl Amides with Alkynes: Direct Synthesis of a 5-HT3 Receptor Antagonist Analogue
  作者：Mao-Gui Huang、Shuai Shi、Ming Li、Yue-Jin Liu、Ming-Hua Zeng

  DOI：10.1021/acs.orglett.1c02502

  日期：2021.9.17

  A cobalt-catalyzed annulation of the C(sp2)–H/N–H bond of indoloamides with alkynes assisted by 8-aminoquinoline is reported for the synthesis of six-membered indololactams. The use of salicylaldehyde as the ligand is crucial for this transformation. The protocol has a broad scope for both alkynes and indoles. Preparing an active Co complex illustrates that salicylaldehyde plays a key role in the C–H

  据报道，在 8-氨基喹啉的辅助下，吲哚酰胺的 C(sp 2 )-H/N-H 键与炔烃的钴催化环化可用于合成六元吲哚内酰胺。使用水杨醛作为配体对于这种转化至关重要。该协议对炔烃和吲哚都有广泛的适用范围。制备活性 Co 复合物说明水杨醛在 C-H 活化步骤中起关键作用。合成应用通过多环 5-HT3 受体拮抗剂的克级反应和一步构建得到证实。
• Weak Directing Group Steered Formal Oxidative [2+2+2]-Cyclization for Selective Benzannulation of Indoles
  作者：Kiran R. Bettadapur、Raja Kapanaiah、Veeranjaneyulu Lanke、Kandikere Ramaiah Prabhu

  DOI：10.1021/acs.joc.7b02719

  日期：2018.2.16

  A double C–H activation and double insertion process to achieve the synthesis benzo[e]indole frameworks has been disclosed. This type of benzannulation is directed by a trifluoromethylketone moiety, which is easy to install on the indole C3-position. Overall the reaction takes places as an oxidative cyclization of two alkynes with the C4–C5 position of indole.

  已公开了双CH活化和双插入过程以实现合成苯并[e]吲哚骨架。这种类型的苯环是由易于安装在吲哚C3位置上的三氟甲基酮部分控制的。总体而言，该反应发生在两个炔烃的C4-C5位置的炔烃的氧化环化反应上。
• Electronic Nature of Ketone Directing Group as a Key To Control C-2 vs C-4 Alkenylation of Indoles
  作者：Veeranjaneyulu Lanke、Kiran R. Bettadapur、Kandikere Ramaiah Prabhu

  DOI：10.1021/acs.orglett.6b02698

  日期：2016.11.4

  A novel mode of achieving site selectivity between C-2 and C-4 positions in the indole framework by altering the property of the ketone directing group is disclosed. Methyl ketone, as directing group, furnishes exclusively C-2 alkenylated product, whereas trifluoromethyl ketone changes the selectivity to C-4, indicating that the electronic nature of the directing group controls the unusual choice between

  公开了通过改变酮指导基团的性质实现在吲哚骨架中C-2和C-4位置之间的位点选择性的新模式。甲基酮作为导向基团仅提供C-2烯基化产物，而三氟甲基酮改变了对C-4的选择性，表明该导向基团的电子性质控制着5元和6元金属环之间的不寻常选择。 。对其他羰基衍生的导向基团的筛选显示强和弱的导向基团表现出相反的选择性。实验控制和氘代实验为提出的机制提供了支持。
• C−H Activation and Cross‐Coupling of Acyclic Aldonitrone
  作者：Jakub Brześkiewicz、Barbara Stańska、Piotr Dąbrowski、Rafał Loska

  DOI：10.1002/ejoc.202001496

  日期：2021.2.5

  Palladium‐catalyzed C(sp2)−H activation of an acyclic, glyoxalate‐derived aldonitrone and its cross‐coupling with a variety of aryl and heteroaryl bromides provides C‐aryl ketonitrones with very high E selectivity.

  钯催化的无环乙二醛基乙二醛腈的C（sp 2）-H活化及其与各种芳基和杂芳基溴化物的交叉偶联为C-芳基酮硝酮提供了很高的E选择性。
• Rhodium(<scp>iii</scp>)-catalyzed C–H activation at the C4-position of indole: switchable hydroarylation and oxidative Heck-type reactions of maleimides
  作者：Mahadev Sharanappa Sherikar、Raja Kapanaiah、Veeranjaneyulu Lanke、Kandikere Ramaiah Prabhu

  DOI：10.1039/c8cc06264a

  日期：——

  leading to novel and switchable functionalization has been reported by employing a weakly co-ordinating COCF3 group as a directing group. An additive plays an important role in switching the selectivity between 1,4-addition products and Heck-type products. An acid additive led to the formation of 1,4-addition products whereas a base additive promotes the formation of Heck-type products. Deuteration

  通过弱配位的COCF 3基团作为指导基团，已报道了Rh（III）催化的C4-位吲哚在CH4上的CH活化，从而导致新颖且可转换的官能化。添加剂在1，4-加成产物和Heck型产物之间切换选择性方面起着重要作用。酸添加剂导致形成1,4-加成产物，而碱添加剂则促进形成Heck型产物。氘代研究和控制实验有助于提出机理。