2922-07-8Relevant articles and documents
A general and efficient synthesis of azaindoles and diazaindoles
Harcken, Christian,Ward, Yancey,Thomson, David,Riether, Doris
, p. 3121 - 3125 (2005)
The DBU-mediated cyclization of ortho-(Boc-amino)alkynyl pyridines, -pyridazines, -pyrimidines and -pyrazines efficiently generates azaindoles and diazaindoles, respectively. The reaction proceeds under mild conditions and in high yields. A variety of fun
Synthesis of Indoles by Reductive Cyclization of Nitro Compounds Using Formate Esters as CO Surrogates
Ahmed Fouad, Manar,Ferretti, Francesco,Formenti, Dario,Milani, Fabio,Ragaini, Fabio
, p. 4876 - 4894 (2021/09/20)
Alkyl and aryl formate esters were evaluated as CO sources in the Pd- and Pd/Ru-catalyzed reductive cyclization of 2-nitrostyrenes to give indoles. Whereas the use of alkyl formates requires the presence of a ruthenium catalyst such as Ru3(CO)12, the reaction with phenyl formate can be performed by using a Pd/phenanthroline complex alone. Phenyl formate was found to be the most effective CO source and the desired products were obtained in excellent yields, often higher than those previously reported using pressurized CO. The reaction tolerates many functional groups, including sensitive ones like a free aldehydic group or a pendant pyrrole. Detailed experiments and kinetic studies allow to conclude that the activation of phenyl formate is base-catalyzed and that the metal doesn't play a role in the decarbonylation step. The reactions can be performed in a single thick-walled glass tube with as little as 0.2 mol-% palladium catalyst and even on a 2 g scale. The same protocol can be extended to other nitro compounds, affording different heterocycles.
Exploring the reactivity of halogen-free aminopyridines in one-pot palladium-catalyzed C–N cross-coupling/C–H functionalization
Santos, A. Sofia,Martins, M. Margarida,Mortinho, Ana C.,Silva, Artur M.S.,Marques, M. Manuel B.
supporting information, (2020/08/13)
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.
Application of Fluorine- And Nitrogen-Walk Approaches: Defining the Structural and Functional Diversity of 2-Phenylindole Class of Cannabinoid 1 Receptor Positive Allosteric Modulators
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.
, p. 542 - 568 (2020/02/04)
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.
Synthesis of N-Heterocycles by Reductive Cyclization of Nitro Compounds using Formate Esters as Carbon Monoxide Surrogates
Formenti, Dario,Ferretti, Francesco,Ragaini, Fabio
, p. 148 - 152 (2017/12/04)
A series of alkyl and aryl formate esters were evaluated as CO sources in the Pd- and Pd/Ru-catalyzed reductive cyclization of substituted nitro compounds to afford heterocycles, especially indoles. Phenyl formate was found to be the most effective, and it allowed the desired products to be obtained in excellent yields, often higher than those previously reported with pressurized CO. Through detailed experiments and kinetic studies, we were able to discern between metal-catalyzed and base-mediated activation of phenyl formate and confirmed that just the base was effective in catalyzing its decarbonylation.
Asymmetric Hydrogenation of Azaindoles: Chemo- and Enantioselective Reduction of Fused Aromatic Ring Systems Consisting of Two Heteroarenes
Makida, Yusuke,Saita, Masahiro,Kuramoto, Takahiro,Ishizuka, Kentaro,Kuwano, Ryoichi
supporting information, p. 11859 - 11862 (2016/11/16)
High enantioselectivity was achieved for the hydrogenation of azaindoles by using the chiral catalyst, which was prepared from [Ru(η3-methallyl)2(cod)] and a trans-chelating bis(phosphine) ligand (PhTRAP). The dearomative reaction exclusively occurred on the five-membered ring, thus giving the corresponding azaindolines with up to 97:3 enantiomer ratio.
Synthesis of Substituted 4-, 5-, 6-, and 7-Azaindoles from Aminopyridines via a Cascade C-N Cross-Coupling/Heck Reaction
Pires, Marina J. D.,Poeira, Diogo L.,Purifica?ao, Sara I.,Marques, M. Manuel B.
supporting information, p. 3250 - 3253 (2016/07/13)
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.
One-pot synthesis of azaindoles via palladium-catalyzed α-heteroarylation of ketone enolates
Spergel, Steven H.,Okoro, Danielle R.,Pitts, William
supporting information; experimental part, p. 5316 - 5319 (2010/10/19)
(Figure presented) A convenient, one-pot method for the construction of a variety of azaindoles using simple ketones and haloaminopyridines is described.
Palladium-catalyzed reductive N-heterocyclization of alkenyl-substituted nitroarenes as a viable method for the preparation of bicyclic pyrrolo-fused heteroaromatic compounds
Gorugantula, Sobha P.,Carrero-Martínez, Grissell M.,Dantale, Shubhada W.,S?derberg, Bj?rn C.G.
experimental part, p. 1800 - 1805 (2010/04/06)
Palladium-catalyzed, carbon monoxide-mediated reductive N-heterocyclization of nitro-heteroaromatic compounds having an alkene adjacent to the nitro-group affords bicyclic pyrrolo-fused heteroaromatic molecules. This type of reaction was used to prepare the fused bicyclo[3.3.0] ring-system: thieno[3,2-b]pyrrole, thieno[2,3-b]pyrrole, furo[2,3-b]pyrrole, pyrrolo[3,2-d]thiazole, and pyrrolo[2,3-d]imidazole and the bicyclo[4.3.0] ring-systems: pyrrolo[3,2-b]pyridine, pyrrolo[2,3-b]pyridine, pyrrolo[3,2-c]pyridine, pyrrolo[2,3-c]pyridine, pyrrolo[3,2-c]pyridazine, and pyrrolo[3,2-d]pyrimidine in 32-94% yield.
A novel one-step synthesis of 2-substituted 6-azaindoles from 3-amino-4-picoline and carboxylic esters
Song, Jinhua J.,Tan, Zhulin,Gallou, Fabrice,Xu, Jinghua,Yee, Nathan K.,Senanayake, Chris H.
, p. 6512 - 6514 (2007/10/03)
Dilithiation of 3-amino-4-picoline (1) was achieved with sec-BuLi at room temperature. Condensation of the resulting dianion (2) with carboxylic esters afforded a wide range of 2-substituted 6-azaindoles in good yields.
