- Activation-free one-pot alkynylation–cyclization synthesis of 2-substituted 4-azaindoles and indoles
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[Figure not available: see fulltext.] 2-Substituted 4-azaindoles and indoles are rapidly and efficiently prepared in an activation-free Pd-catalyzed alkynylation–cyclization sequence starting from 3-amino-2-bromopyridine or o-bromoaniline and terminal alkynes in a one-pot fashion.
- Lessing, Timo,Müller, Thomas J. J.
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- Exploring the reactivity of halogen-free aminopyridines in one-pot palladium-catalyzed C–N cross-coupling/C–H functionalization
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Aminopyridines are key building blocks for the synthesis of bioactive N-heterocyclic compounds such as azaindoles and imidazopyridines. However, the functionalization of aminopyridines is challenging, due to their electronic properties and coordination with metals. Herein we describe a reactivity study of aminopyridines under palladium-catalyzed reaction conditions. Several aminopyridines underwent a one-pot Pd-catalyzed C–N cross coupling reaction/C–H functionalization sequence affording azaindoles. The role of additives, ligands, and bases was investigated. This work consists of a platform for future studies on aminopyridines involving metal-catalyzed reactions and represents the first report on the direct conversion of non-halogenated aminopyridines into azaindoles via Pd-catalyzed C–H functionalization reactions.
- Santos, A. Sofia,Martins, M. Margarida,Mortinho, Ana C.,Silva, Artur M.S.,Marques, M. Manuel B.
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supporting information
(2020/08/13)
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- Application of Fluorine- And Nitrogen-Walk Approaches: Defining the Structural and Functional Diversity of 2-Phenylindole Class of Cannabinoid 1 Receptor Positive Allosteric Modulators
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Cannabinoid 1 receptor (CB1R) allosteric ligands hold a far-reaching therapeutic promise. We report the application of fluoro- and nitrogen-walk approaches to enhance the drug-like properties of GAT211, a prototype CB1R allosteric agonist-positive allosteric modulator (ago-PAM). Several analogs exhibited improved functional potency (cAMP, β-arrestin 2), metabolic stability, and aqueous solubility. Two key analogs, GAT591 (6r) and GAT593 (6s), exhibited augmented allosteric-agonist and PAM activities in neuronal cultures, improved metabolic stability, and enhanced orthosteric agonist binding (CP55,940). Both analogs also exhibited good analgesic potency in the CFA inflammatory-pain model with longer duration of action over GAT211 while being devoid of adverse cannabimimetic effects. Another analog, GAT592 (9j), exhibited moderate ago-PAM potency and improved aqueous solubility with therapeutic reduction of intraocular pressure in murine glaucoma models. The SAR findings and the enhanced allosteric activity in this class of allosteric modulators were accounted for in our recently developed computational model for CB1R allosteric activation and positive allosteric modulation.
- Garai, Sumanta,Kulkarni, Pushkar M.,Schaffer, Peter C.,Leo, Luciana M.,Brandt, Asher L.,Zagzoog, Ayat,Black, Tallan,Lin, Xiaoyan,Hurst, Dow P.,Janero, David R.,Abood, Mary E.,Zimmowitch, Anaelle,Straiker, Alex,Pertwee, Roger G.,Kelly, Melanie,Szczesniak, Anna-Maria,Denovan-Wright, Eileen M.,Mackie, Ken,Hohmann, Andrea G.,Reggio, Patricia H.,Laprairie, Robert B.,Thakur, Ganesh A.
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p. 542 - 568
(2020/02/04)
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- Chelation-assisted C-S activation/cascade heteroannulation of pyridine-2-thione derivatives in Pd-catalyzed cross-coupling reaction with alkynes
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Ortho-chelation assistance was proved to be crucial for the success of the desulfitative Sonogashira cross-coupling reaction of thioamide-type pyridine derivatives and alkynes. Corresponding alkynylated products were obtained with moderate to excellent yields. Thanks to this reaction, furo[3,2-b]pyridine and 1H-pyrrolo[3,2-b]pyridine derivatives were synthesized through a one-pot cross-coupling reaction/heteroannulation sequence.
- Zou, Wenxing,Huang, Zongze,Jiang, Kang,Wu, You,Xue, Yuqing,Suzenet, Franck,Sun, Qi,Guillaumet, Gérald
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p. 5485 - 5492
(2017/08/22)
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- Synthesis of Substituted 4-, 5-, 6-, and 7-Azaindoles from Aminopyridines via a Cascade C-N Cross-Coupling/Heck Reaction
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A practical palladium-catalyzed cascade C-N cross-coupling/Heck reaction of alkenyl bromides with amino-o-bromopyridines is described for a straightforward synthesis of substituted 4-, 5-, 6-, and 7-azaindoles using a Pd2(dba)3/XPhos/t-BuONa system. This procedure consists of the first cascade C-N cross-coupling/Heck approach toward all four azaindole isomers from available aminopyridines. The scope of the reaction was investigated and several alkenyl bromides were used, allowing access to different substituted azaindoles. This protocol was further explored for N-substituted amino-o-bromopyridines.
- Pires, Marina J. D.,Poeira, Diogo L.,Purifica?ao, Sara I.,Marques, M. Manuel B.
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supporting information
p. 3250 - 3253
(2016/07/13)
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- Azaindole synthesis through dual activation catalysis with N-heterocyclic carbenes
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A convergent, transition-metal-free synthesis of 2-aryl-azaindoles has been developed. The interception of a reactive aza-ortho-azaquinone methide intermediate by an acyl anion equivalent generated through carbene catalysis provides high yields, a wide substrate scope, and the synthesis of previously inaccessible azaindoles.
- Sharma, Hayden A.,Todd Hovey,Scheidt, Karl A.
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p. 9283 - 9286
(2016/07/25)
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- Pd-Catalyzed cascade reaction for the synthesis of 2-substituted indoles
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An efficient cascade methodology toward the synthesis of 2-substituted indoles has been developed. The transformation proceeds via a palladium-catalyzed cross-coupling reaction of o-nitrobenzyl cyanides with boronic acids. The use of Fe as co-catalyst during the course of reaction employs significant enhancement in reaction rates. The developed protocol allows for the unprecedented use of arylboronic acids as coupling partners for constructing 2-substituted indoles.
- Jadhav, Jagannath,Gaikwad, Vipul,Kurane, Rajanikant,Salunkhe, Rajashri,Rashinkar, Gajanan
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p. 2511 - 2515,5
(2012/12/11)
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- Pd-Catalyzed cascade reaction for the synthesis of 2-substituted indoles
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An efficient cascade methodology toward the synthesis of 2-substituted indoles has been developed. The transformation proceeds via a palladium-catalyzed cross-coupling reaction of o-nitrobenzyl cyanides with boronic acids. The use of Fe as co-catalyst during the course of reaction employs significant enhancement in reaction rates. The developed protocol allows for the unprecedented use of arylboronic acids as coupling partners for constructing 2-substituted indoles. Georg Thieme Verlag Stuttgart · New York.
- Jadhav, Jagannath,Gaikwad, Vipul,Kurane, Rajanikant,Salunkhe, Rajashri,Rashinkar, Gajanan
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p. 2511 - 2515
(2013/01/13)
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- One-pot synthesis of azaindoles via palladium-catalyzed α-heteroarylation of ketone enolates
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(Figure presented) A convenient, one-pot method for the construction of a variety of azaindoles using simple ketones and haloaminopyridines is described.
- Spergel, Steven H.,Okoro, Danielle R.,Pitts, William
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supporting information; experimental part
p. 5316 - 5319
(2010/10/19)
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- 2-SUBSTITUTED AZAIN DOLES AND 2 SUBSTITUTED THIENOPYRROLES, THEIR PRECURSORS AND NOVEL PROCESSES FOR THE PREPARATION THEREOF
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The present invention relates generally to processes for the chemical synthesis of azaindole and thienopyrrole compounds, in particular azaindole and thienopyrrole compounds that are substituted at the 2-position of the azaindole or thienopyrrole ring, an
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Page/Page column 138
(2010/11/30)
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- Facile synthesis of 2-substituted 4-azaindoles
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A novel and efficient strategy for the synthesis of 2-substituted 4-azaindoles from 2-chloro-3-nitropyridine through Pd-catalyzed Sonogashira cross-coupling, followed by reduction and heteroannulation on t-BuOK, is reported. Copyright Taylor & Francis Group, LLC.
- Sun, Li-Ping,Wang, Jin-Xin
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p. 2187 - 2193
(2008/02/05)
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- A general modular method of azaindole and thienopyrrole synthesis via Pd-catalyzed tandem couplings of gem-dichloroolefins
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(Chemical Equation Presented) A palladium-catalyzed reaction of gem-dichloroolefins and a boronic acid via a tandem intramolecular C-N and intermolecular Suzuki coupling process gave corresponding substituted azaindoles or thienopyrroles. This method is a
- Fang, Yuan-Qing,Yuen, Josephine,Lautens, Mark
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p. 5152 - 5160
(2008/02/07)
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- AMIDE DERIVATIVES AND DRUGS
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The present invention provides an amide derivative represented by the following formula [1]: wherein n represents 0 or 1; X represents CR4 or N; Y represents CR6 or N; Z represents CR7 or N; R1 and R2 may be the same or different and each represents hydrogen, optionally substituted alkyl, acyl, optionally substituted aryl, or an optionally substituted aromatic heterocyclic group; R4, R5, R6 and R7 may be the same or different and each represents hydrogen, halogen, hydroxy, amino, alkyl, haloalkyl, alkoxy, monoalkylamino, dialkylamino, arylalkyl, cyano, or nitro; and R3 represents optionally substituted alkylamino, optionally substituted arylamino, or optionally substituted cyclic amino, or a pharmaceutically acceptable salt thereof, and a pharmaceutical composition comprising them as an active ingredient. The compound of the present invention is useful as a TGF-β inhibitor.
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- Synthesis of polyfunctional indoles and related heterocycles mediated by cesium and potassium bases
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A general preparation of 2-substituted indoles starting from functionalized 2-alkynylanilines has been developed. This base mediated reaction has also been used to synthesize the heterocyclic core of the marine alkaloid hinckdentine A. Furthermore the reaction was successfully adapted to the solid phase. Benzofurans and isoindolones could also be prepared with this method.
- Koradin, Christopher,Dohle, Wolfgang,Rodriguez, Alain L.,Schmid, Bertram,Knochel, Paul
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p. 1571 - 1587
(2007/10/03)
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- Synthesis of 2-aryl-1-hydroxyazaindoles and 2-arylazaindoles via oxidation of o-hydroxyaminostyrylpyridines
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2-Aryl-1-hydroxyazaindoles (pyrrolopyridin-1-ols) are prepared via an oxidation/cyclization of o-hydroxyaminostyrylpyridines with DDQ. Reduction of the N-OH bond affords the corresponding 2-arylazaindoles (1H-pyrrolopyridines). The scope of the cyclization is explored via (i) the condensation of 4-methyl-3-nitropyridine with various aryl aldehydes to afford 2-aryl substituted 6-azaindoles and, (ii) the synthesis of 2-phenyl-4-, 5- and 7-azaindoles.
- Kuzmich, Daniel,Mulrooney, Carol
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p. 1671 - 1678
(2007/10/03)
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- Versatile indole synthesis by a 5-endo-dig cyclization mediated by potassium or cesium bases
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A mild route to indoles by cyclization of 2-(1-alkynyl)anilines is offered by the use of simple bases such as KOtBu, KH, or CsOtBu and N-methylpyrrolidinone (NMP) at room temperature. The reaction has a broad scope and allows the preparation of various functionalized indoles as well as new aza-or diazaindoles in excellent yields [see, for example, Eq. (1)].
- Rodriguez, Alain Louis,Koradin, Christopher,Dohle, Wolfgang,Knochel, Paul
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p. 2488 - 2490
(2007/10/03)
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- Catalytic dehydrocyclization of azomethines. Synthesis of substituted indoles and 4(5)-azaindoles
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Catalytic dehydrocydization of azomethines obtained by condensation of p-toluidine and also 3(4)-aminopyridines with methyl aryl ketones leads to substituted indoles and pyrrolopyridine isomers with the nitrogen atom at different positions in the six-memb
- Zvolinskii,Pleshakov,Prostakov
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p. 202 - 205
(2007/10/03)
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