66616-69-1Relevant academic research and scientific papers
Synthesis method for preparing 2-substituted indole derivative
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Paragraph 0079-0082, (2019/05/28)
The invention relates to a synthesis method for preparing a 2-substituted indole derivative. The method includes the following steps: mixing aromatic amine compounds (I), ketone compounds (II) and a drying agent in an organic solvent; adding a palladium catalyst; and reacting in an aerobic weak acid environment to prepare the indole compounds (III). (I), (II) and (III) are as shown in the specification, wherein R1 is selected from hydrogen, C1-C6 alkyl, C1-C6 alkoxy, C1-C6 alkanoyl, C2-C6 alkenyl, C2-C6 alkynyl, halogen, hydroxyl, substituted or unsubstituted amino, substituted or unsubstituted phenyl, pyridyl and heterocyclic aryl; (I) can be pyridylamine, pyrimidylamine, pyridazinam or pyrazinamide which may further be substituted or unsubstituted; and the substituents are selected fromone or more C1-C6 alkyl, C1-C6 alkoxy, C1-C6 alkanoyl, C2-C6 alkenyl, C2-C6 alkynyl, halogen, hydroxyl, amino; and R2 is selected from C1-C6 alkyl, formate groups or C1-C6 alkylamide groups.
Carboxylic Acid-Promoted Single-Step Indole Construction from Simple Anilines and Ketones via Aerobic Cross-Dehydrogenative Coupling
Ren, Long,Nan, Guanglei,Wang, Yongcheng,Xiao, Zhiyan
, p. 14472 - 14488 (2018/11/23)
The cross-dehydrogenative coupling (CDC) reaction is an efficient strategy for indole synthesis. However, most CDC methods require special substrates, and the presence of inherent groups limits the versatility for further transformation. A carboxylic acid-promoted aerobic catalytic system is developed herein for a single-step synthesis of indoles from simple anilines and ketones. This versatile system is featured by the broad substrate scope and the use of ambient oxygen as an oxidant and is convenient and economical for both laboratory and industry applications. The existence of the labile hydrogen at C-3 and the highly transformable carbonyl at C-2 makes the indoles versatile building blocks for organic synthesis in different contexts. Computational studies based on the density functional theory (DFT) suggest that the rate-determining step is carboxylic acid-assisted condensation of the substrates, rather than the functionalization of aryl C-H. Accordingly, a pathway via imine intermediates is deemed to be the preferred mechanism. In contrast to the general deduction, the in situ formed imine, instead of its enamine isomer, is believed to be involved in the first ligand exchange and later carbopalladation of the α-Me, which shed new light on this indolization mechanism.
Synthesis of Indole-2-carboxylate Derivatives via Palladium-Catalyzed Aerobic Amination of Aryl C-H Bonds
Clagg, Kyle,Hou, Haiyun,Weinstein, Adam B.,Russell, David,Stahl, Shannon S.,Koenig, Stefan G.
, p. 3586 - 3589 (2016/08/16)
A direct oxidative C-H amination affording 1-acetyl indolecarboxylates starting from 2-acetamido-3-arylacrylates has been achieved. Indole-2-carboxylates can be targeted with a straightforward deacetylation of the initial reaction products. The C-H amination reaction is carried out using a catalytic Pd(II) source with oxygen as the terminal oxidant. The scope and application of this chemistry is demonstrated with good to high yields for numerous electron-rich and electron-poor substrates. Further reaction of selected products via Suzuki arylation and deacetylation provides access to highly functionalized indole structures.
Probing the molecular and structural elements of ligands binding to the active site versus an allosteric pocket of the human farnesyl pyrophosphate synthase
Gritzalis, Dimitrios,Park, Jaeok,Chiu, Wei,Cho, Hyungjun,Lin, Yih-Shyan,De Schutter, Joris W.,Lacbay, Cyrus M.,Zielinski, Michal,Berghuis, Albert M.,Tsantrizos, Youla S.
, p. 1117 - 1123 (2015/02/19)
In order to explore the interactions of bisphosphonate ligands with the active site and an allosteric pocket of the human farnesyl pyrophosphate synthase (hFPPS), substituted indole and azabenzimidazole bisphosphonates were designed as chameleon ligands. NMR and crystallographic studies revealed that these compounds can occupy both sub-pockets of the active site cavity, as well as the allosteric pocket of hFPPS in the presence of the enzyme's Mg2+ ion cofactor. These results are consistent with the previously proposed hypothesis that the allosteric pocket of hFPPS, located near the active site, plays a feed-back regulatory role for this enzyme.
Indoles via Knoevenagel-Hemetsberger reaction sequence
Heaner Iv, William L.,Gelbaum, Carol S.,Gelbaum, Leslie,Pollet, Pamela,Richman, Kent W.,Dubay, William,Butler, Jeffrey D.,Wells, Gregory,Liotta, Charles L.
, p. 13232 - 13242 (2013/09/02)
A series of substituted indoles have been synthesized by the sequential reaction of aromatic aldehydes with ethyl azidoacetate in the presence of sodium ethoxide to form the corresponding ethyl α-azido-β-arylacrylates (Knoevenagel process) followed by a solvent mediated thermolysis (Hemetsberger process). The isolated yields of the ethyl α-azido-β-arylacrylates were significantly increased when employing the sacrificial electrophile ethyl trifluoroacetate. 1H NMR and coupled 1H-13C NMR analysis of the ethyl α-azido-β-arylacrylates indicate that the condensation is stereospecific - only the Z-isomer could be detected. Solvent mediated thermal treatment of the meta-substituted ethyl α-azido-β- arylacrylates resulted in the formation of both the 5- and 7- substituted indoles - the 5-regioisomer being slightly favored over the 7-regioisomer. Analogous thermal treatment of (2Z, 2Z′)-diethyl 3,3′-(1,3- phenylene)bis(2-azidoacrylate) and (2Z, 2Z′)-diethyl 3,3′-(1,4- phenylene)bis(2-azidoacrylate) exclusively produced pyrroloindoles, diethyl 1,5-dihydropyrrolo[2,3-f]indole-2,6-dicarboxylate and diethyl 1,5-dihydropyrrolo[2,3-f]indole-2,6-dicarboxylate, respectively. Results are also reported which indicate that the α-azido-β-arylacrylates can be used in the subsequent Hemetsberger indolization process without prior purification.
Room-temperature Suzuki-Miyaura coupling of heteroaryl chlorides and tosylates
Yang, Junfeng,Liu, Sijia,Zheng, Jian-Feng,Zhou, Jianrong
supporting information, p. 6248 - 6259,12 (2020/09/16)
Suzuki-Miyaura coupling of heteroaryls is an important method for the preparation of compound libraries for medicinal chemistry and materials research. Although many catalysts have been developed, none of them have been generally applicable to the coupling reactions of heteroaryl chlorides and tosylates at room temperature. We discovered that a catalyst combination of Pd(OAc)2 and XPhos (2-dicyclohexylphosphanyl-2',4',6'- triisopropylbiphenyl) could efficiently catalyze these couplings. Besides the choice of catalyst, the use of hydroxide bases in an aqueous alcoholic solvent was essential for fast couplings. These conditions promoted fast release of active catalyst (XPhos)Pd0, and accelerated the transmetalation in the catalytic cycle. Most of the major families of heteroaryl chlorides (31 examples) and tosylates (17 examples) reached full conversion within minutes to hours at room temperature. The method could be easily scaled up for gram-scale synthesis. Furthermore, we examined the relative reactivity of coupling partners in whole reactions. Electron-rich heteroaryl chlorides and tosylates reacted more slowly than electron-deficient ones, in the order of indole, pyrrole furan, thiophene > pyridine. Similarly, electron-deficient arylboronic acids were less reactive than electron-neutral and electron-rich ones. The reactivity trends from this study can help to choose appropriate coupling partners for Suzuki reactions.
Some new derivatives of 5-aryl-,2,5-diaryland 2-ethoxycarbonyl-5-aryl- indoles
Chikvaidze, Ioseb Sh.,Barbakadze, Nana N.,Samsoniya, Shota A.
experimental part, p. 143 - 154 (2012/05/05)
Some derivatives of 5-aryl-, 2.5-diaryl-, and 2-ethoxycarbonyl-5-aryl- indoles are synthesized. Some reactions of ethyl 5-phenylindole-2-carboxylate are described. It is revealed that an α-ethoxycarbonyl group has a steric and electron-acceptor influence on indole substitution reactions. The structures of all novel compounds are confirmed by IR, UV, 1H NMR, 13C NMR and elemental analyses. ARKAT-USA, Inc.
Fragment-based discovery of indole inhibitors of matrix metalloproteinase-13
Taylor, Steven J.,Abeywardane, Asitha,Liang, Shuang,Muegge, Ingo,Padyana, Anil K.,Xiong, Zhaoming,Hill-Drzewi, Melissa,Farmer, Bennett,Li, Xiang,Collins, Brandon,Li, John Xiang,Heim-Riether, Alexander,Proudfoot, John,Zhang, Qiang,Goldberg, Daniel,Zuvela-Jelaska, Ljiljana,Zaher, Hani,Li, Jun,Farrow, Neil A.
experimental part, p. 8174 - 8187 (2012/01/13)
Matrix metalloproteases (MMPs) play an important role in cartilage homeostasis under both normal and inflamed disease states and, thus, have become attractive targets for the treatment of arthritic diseases. Herein, we describe the identification of a pot
Carboxylic acid derivatives as IP antagonists
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, (2008/06/13)
This invention relates to compounds which are generally IP receptor antagonists and which are represented by Formula I: wherein: R1, R2, and R3 are each independently in each occurrence aryl or heteroaryl; R4 is
