{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,12]],"date-time":"2025-10-12T02:26:54Z","timestamp":1760236014397,"version":"build-2065373602"},"reference-count":97,"publisher":"MDPI AG","issue":"20","license":[{"start":{"date-parts":[[2021,10,19]],"date-time":"2021-10-19T00:00:00Z","timestamp":1634601600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100007525","name":"University of Rennes 1","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100007525","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004794","name":"French National Centre for Scientific Research","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004794","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100008530","name":"Fonds Europ\u00e9en de D\u00e9veloppement R\u00e9gional","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100008530","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Thermo Fischer"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Five protocols were first compared for the copper-catalyzed C-N bond formation between 7-azaindole and aryl\/heteroaryl iodides\/bromides. The 1-arylated 7-azaindoles thus obtained were subjected to deprotometalation-iodolysis sequences using lithium 2,2,6,6-tetramethylpiperidide as the base and the corresponding zinc diamide as an in situ trap. The reactivity of the substrate was discussed in light of the calculated atomic charges and the pKa values. The behavior of the 1-arylated 7-azaindoles in direct iodination was then studied, and the results explained by considering the HOMO orbital coefficients and the atomic charges. Finally, some of the iodides generated, generally original, were involved in the N-arylation of indole. While crystallographic data were collected for fifteen of the synthesized compounds, biological properties (antimicrobial, antifungal and antioxidant activity) were evaluated for others.<\/jats:p>","DOI":"10.3390\/molecules26206314","type":"journal-article","created":{"date-parts":[[2021,10,20]],"date-time":"2021-10-20T03:01:13Z","timestamp":1634698873000},"page":"6314","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Deprotometalation-Iodolysis and Direct Iodination of 1-Arylated 7-Azaindoles: Reactivity Studies and Molecule Properties"],"prefix":"10.3390","volume":"26","author":[{"given":"Mohamed Yacine","family":"Ameur Messaoud","sequence":"first","affiliation":[{"name":"Institut des Sciences Chimiques de Rennes\u2013UMR 6226, University of Rennes, CNRS, ISCR, 35000 Rennes, France"},{"name":"Laboratoire de Synth\u00e8se Organique Appliqu\u00e9e, Facult\u00e9 des Sciences Exactes et Appliqu\u00e9es, Universit\u00e9 d\u2019Oran 1 Ahmed Ben Bella, BP 1524 El M\u2019Naouer, Oran 31000, Algeria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ghenia","family":"Bentabed-Ababsa","sequence":"additional","affiliation":[{"name":"Laboratoire de Synth\u00e8se Organique Appliqu\u00e9e, Facult\u00e9 des Sciences Exactes et Appliqu\u00e9es, Universit\u00e9 d\u2019Oran 1 Ahmed Ben Bella, BP 1524 El M\u2019Naouer, Oran 31000, Algeria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6502-3110","authenticated-orcid":false,"given":"Ziad","family":"Fajloun","sequence":"additional","affiliation":[{"name":"Laboratory of Applied Biotechnology (LBA3B), Azm Center for Research in Biotechnology and Its Applications, EDST, Lebanese University, Tripoli 1300, Lebanon"},{"name":"Faculty of Sciences 3, Campus Michel Slayman, Lebanese University, Tripoli 1352, Lebanon"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Monzer","family":"Hamze","sequence":"additional","affiliation":[{"name":"Laboratoire Microbiologie, Sant\u00e9 et Environnement, Doctoral School of Sciences and Technology, Faculty of Public Health, Lebanese University, Tripoli 1300, Lebanon"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yury S.","family":"Halauko","sequence":"additional","affiliation":[{"name":"UNESCO Chair of Belarusian State University, 220030 Minsk, Belarus"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Oleg A.","family":"Ivashkevich","sequence":"additional","affiliation":[{"name":"Research Institute for Physico-Chemical Problems, Belarusian State University, 220030 Minsk, Belarus"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vadim E.","family":"Matulis","sequence":"additional","affiliation":[{"name":"Research Institute for Physico-Chemical Problems, Belarusian State University, 220030 Minsk, Belarus"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6088-4472","authenticated-orcid":false,"given":"Thierry","family":"Roisnel","sequence":"additional","affiliation":[{"name":"Institut des Sciences Chimiques de Rennes\u2013UMR 6226, University of Rennes, CNRS, ISCR, 35000 Rennes, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vincent","family":"Dorcet","sequence":"additional","affiliation":[{"name":"Institut des Sciences Chimiques de Rennes\u2013UMR 6226, University of Rennes, CNRS, ISCR, 35000 Rennes, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3693-8861","authenticated-orcid":false,"given":"Florence","family":"Mongin","sequence":"additional","affiliation":[{"name":"Institut des Sciences Chimiques de Rennes\u2013UMR 6226, University of Rennes, CNRS, ISCR, 35000 Rennes, France"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2021,10,19]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"471","DOI":"10.1007\/BF02219249","article-title":"Chemistry of the azaindoles (review)","volume":"28","author":"Prokopov","year":"1994","journal-title":"Pharm. Chem. J."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"471","DOI":"10.2174\/1385272013375427","article-title":"Synthesis and reactivity of 7-azaindoles (1H-pyrrolo[2,3-b]pyridines)","volume":"5","author":"Joseph","year":"2001","journal-title":"Curr. Org. Chem."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1120","DOI":"10.1039\/b607868k","article-title":"Organometallic methods for the synthesis and functionalization of azaindoles","volume":"36","author":"Song","year":"2007","journal-title":"Chem. Soc. Rev."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1031","DOI":"10.1016\/j.tet.2006.09.067","article-title":"Synthesis and reactivity of 7-azaindole (1H-pyrrolo[2,3-b]pyridine)","volume":"63","author":"Popowycz","year":"2007","journal-title":"Tetrahedron"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"4767","DOI":"10.1016\/j.tet.2013.03.081","article-title":"Recent advances in the synthesis and properties of 4-, 5-, 6- or 7-azaindoles","volume":"69","author":"Routier","year":"2013","journal-title":"Tetrahedron"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"19935","DOI":"10.3390\/molecules191219935","article-title":"The azaindole framework in the design of kinase inhibitors","volume":"19","author":"Buron","year":"2014","journal-title":"Molecules"},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Santos, A.S., Mortinho, A.C., and Marques, M.M.B. (2018). Metal-catalyzed cross-coupling reactions on azaindole synthesis and functionalization. Molecules, 23.","DOI":"10.3390\/molecules23102673"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"11749","DOI":"10.1039\/D0CC04264A","article-title":"Recent advances in the global ring functionalization of 7-azaindoles","volume":"56","author":"Kannaboina","year":"2020","journal-title":"Chem. Commun."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"737","DOI":"10.1021\/jm700940h","article-title":"Meriolins (3-(pyrimidin-4-yl)-7-azaindoles): Synthesis, kinase inhibitory activity, cellular effects, and structure of a CDK2\/cyclin A\/meriolin complex","volume":"51","author":"Echalier","year":"2008","journal-title":"J. Med. Chem."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1484","DOI":"10.1093\/neuonc\/nou102","article-title":"Impact of meriolins, a new class of cyclin-dependent kinase inhibitors, on malignant glioma proliferation and neo-angiogenesis","volume":"16","author":"Jarry","year":"2014","journal-title":"Neuro-Oncol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1808","DOI":"10.1158\/1535-7163.MCT-09-0041","article-title":"GSK1070916, a potent Aurora B\/C kinase inhibitor with broad antitumor activity in tissue culture cells and human tumor xenograft models","volume":"8","author":"Hardwicke","year":"2009","journal-title":"Mol. Cancer Ther."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"3142","DOI":"10.1039\/c001897j","article-title":"Luminescence and reactivity of 7-azaindole derivatives and complexes","volume":"39","author":"Zhao","year":"2010","journal-title":"Chem. Soc. Rev."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"3018","DOI":"10.1021\/acs.orglett.5b01228","article-title":"Rhodium(III)-catalyzed oxidative annulation of 7-azaindoles and alkynes via double C-H activation","volume":"17","author":"Li","year":"2015","journal-title":"Org. Lett."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"5214","DOI":"10.1039\/C6OB00730A","article-title":"A unique annulation of 7-azaindoles with alkenyl esters to produce \u03c0-conjugated 7-azaindole derivatives","volume":"14","author":"Li","year":"2016","journal-title":"Org. Biomol. Chem."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"48205","DOI":"10.1039\/C6RA07478B","article-title":"Rh(iii)-catalyzed c-h oxidative ortho-olefination of arenes using 7-azaindole as a directing group and utilization in the construction of new tetracyclic heterocycles containing a 7-azaindole skeleton","volume":"6","author":"Liu","year":"2016","journal-title":"RSC Adv."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"3471","DOI":"10.1002\/adsc.201700800","article-title":"Site-selective rhodium(iii)-catalyzed c-h amination of 7-azaindoles with anthranils: Synthesis and anticancer evaluation","volume":"359","author":"Jeon","year":"2017","journal-title":"Adv. Synth. Catal."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"4197","DOI":"10.1002\/ejoc.201800764","article-title":"Metal-free [3+2] tandem cyclization synthesis of unique 11h-pyrido[3\u2032,2\u2032:4,5]pyrrolo [3,2-b] indolizine from 7-azaindoles and pyridotriazoles","volume":"2018","author":"Zhang","year":"2018","journal-title":"Eur. J. Org. Chem."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"6509","DOI":"10.1021\/acs.chemrev.9b00073","article-title":"Design and optimization of catalysts based on mechanistic insights derived from quantum chemical reaction modeling","volume":"119","author":"Ahn","year":"2019","journal-title":"Chem. Rev."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"14198","DOI":"10.1021\/jacs.6b08895","article-title":"Computer-assisted design of ionic liquids for efficient synthesis of 3(2h)-furanones: A domino reaction triggered by CO2","volume":"138","author":"Chen","year":"2016","journal-title":"J. Am. Chem. Soc."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"323","DOI":"10.2174\/157019308786242133","article-title":"Copper(I) catalyzed N-arylation of azoles, the recent developments","volume":"5","author":"Sorokin","year":"2008","journal-title":"Mini-Rev. Org. Chem."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"6954","DOI":"10.1002\/anie.200804497","article-title":"Catalytic C\u2013C, C\u2013N, and C\u2013O Ullmann-type coupling reactions","volume":"48","author":"Monnier","year":"2009","journal-title":"Angew. Chem. Int. Ed."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"7753","DOI":"10.1021\/om300683c","article-title":"The complementary competitors: Palladium and copper in C\u2013N cross-coupling reactions","volume":"31","author":"Beletskaya","year":"2012","journal-title":"Organometallics"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"9283","DOI":"10.1039\/c3cs60228a","article-title":"C\u2013N bond forming cross-coupling reactions: An overview","volume":"42","author":"Bariwal","year":"2013","journal-title":"Chem. Soc. Rev."},{"key":"ref_24","first-page":"173","article-title":"Copper-catalyzed C(aryl)\u2013N bond formation","volume":"46","author":"Monnier","year":"2013","journal-title":"Top. Organomet. Chem."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"3525","DOI":"10.1039\/C3CS60289C","article-title":"Copper catalysed Ullmann type chemistry: From mechanistic aspects to modern development","volume":"43","author":"Sambiagio","year":"2014","journal-title":"Chem. Soc. Rev."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"131680","DOI":"10.1016\/j.tet.2020.131680","article-title":"Efficient copper-catalyzed cross-coupling of nitrogen nucleophiles with N,N-dibenzyl-4-iodobenzenesulfonamide and its application in the synthesis of celecoxib intermediate","volume":"76","author":"Yong","year":"2020","journal-title":"Tetrahedron"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1253","DOI":"10.1002\/adsc.200700535","article-title":"Highly practical \u201cligand-free-like\u201d copper-catalyzed N-arylation of azoles in lower nitrile solvents","volume":"350","author":"Zhu","year":"2008","journal-title":"Adv. Synth. Catal."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"4831","DOI":"10.1016\/j.tetlet.2007.05.062","article-title":"N-arylation of azaindoles in LiCl-mediated catalytic CuI reactions","volume":"48","author":"Hong","year":"2007","journal-title":"Tetrahedron Lett."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"5578","DOI":"10.1021\/jo049658b","article-title":"Copper-diamine-catalyzed N-arylation of pyrroles, pyrazoles, indazoles, imidazoles, and triazoles","volume":"69","author":"Antilla","year":"2004","journal-title":"J. Org. Chem."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"7279","DOI":"10.1016\/j.tet.2013.06.095","article-title":"Ligand-free Cu2O-catalyzed cross coupling of nitrogen heterocycles with iodopyridines","volume":"69","author":"Teo","year":"2013","journal-title":"Tetrahedron"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"4820","DOI":"10.1016\/j.tet.2011.05.022","article-title":"N-arylation of carbazole by microwave-assisted ligand-free catalytic CuI reaction","volume":"67","author":"Kwon","year":"2011","journal-title":"Tetrahedron"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"15928","DOI":"10.1039\/D0NJ03470C","article-title":"Iodoferrocene as a partner in N-arylation of amides","volume":"44","author":"Kadari","year":"2020","journal-title":"New J. Chem."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"377","DOI":"10.1002\/ejic.202000904","article-title":"On the N-arylation of acetamide using 2-, 3- and 1\u2032-substituted iodoferrocenes","volume":"2021","author":"Kadari","year":"2021","journal-title":"Eur. J. Inorg. Chem."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"3637","DOI":"10.1016\/S0040-4020(97)00107-5","article-title":"Synthesis of 2-substituted-1H-pyrrolo[2,3-b]pyridines: Preparation of 7-azaolivacine analog and 7-azaindolopyridopyrimidine derivatives","volume":"53","author":"Desarbre","year":"1997","journal-title":"Tetrahedron"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"3653","DOI":"10.1021\/jo00885a001","article-title":"Directed metalation reactions. 6. Competition of substituents for ortho direction of metalation in substituted anisoles","volume":"41","author":"Slocum","year":"1976","journal-title":"J. Org. Chem."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"4635","DOI":"10.1002\/ejoc.200700525","article-title":"Fluorous synthesis of yuehchukene by alpha-lithiation of perfluoroalkyl-tagged 1-(arylsulfonyl)indole with mesityllithium","volume":"2007","author":"Naka","year":"2007","journal-title":"Eur. J. Org. Chem."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"6808","DOI":"10.1021\/ja00281a061","article-title":"Carbon dioxide: A reagent for simultaneous protection of nucleophilic centers and the activation of alternative locations to electrophilic attack. V. Activation of the 2-alkyl group of a 2-alkylindole toward proton loss and subsequent electrophilic substitution","volume":"108","author":"Katritzky","year":"1986","journal-title":"J. Am. Chem. Soc."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"585","DOI":"10.1016\/S0960-894X(99)00025-6","article-title":"Synthesis and SAR of 2- and 3-substituted 7-azaindoles as potential dopamine D4 ligands","volume":"9","author":"Curtis","year":"1999","journal-title":"Bioorg. Med. Chem. Lett."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1787","DOI":"10.1002\/hlca.200890191","article-title":"Synthesis and cytotoxicity studies of new (dimethylamino)-functionalized and 7-azaindole-substituted \u2018titanocene\u2019 anticancer agents (7-azaindole = 1H-pyrrolo[2,3-b]pyridine)","volume":"91","author":"Hogan","year":"2008","journal-title":"Helv. Chim. Acta"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1160","DOI":"10.1021\/jm3016014","article-title":"Fragment-based discovery of new highly substituted 1H-pyrrolo[2,3-b]- and 3H-imidazolo[4,5-b]-pyridines as focal adhesion kinase inhibitors","volume":"56","author":"Heinrich","year":"2013","journal-title":"J. Med. Chem."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"4636","DOI":"10.1021\/acs.jmedchem.7b00178","article-title":"Trisubstituted imidazoles with a rigidized hinge binding motif act as single digit nm inhibitors of clinically relevant egfr l858r\/t790m and l858r\/t790m\/c797s mutants: An example of target hopping","volume":"60","author":"Juchum","year":"2017","journal-title":"J. Med. Chem."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"2317","DOI":"10.1016\/j.tetlet.2004.01.122","article-title":"Synthesis of functionalized 7-azaindoles via directed ortho-metalations","volume":"45","author":"Thibault","year":"2004","journal-title":"Tetrahedron Lett."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"2722","DOI":"10.1002\/anie.201108016","article-title":"In situ anionic shielding for regioselective metalation: Directed peri and iterative metalation routes to polyfunctionalized 7-azaindoles","volume":"51","author":"Schneider","year":"2012","journal-title":"Angew. Chem. Int. Ed."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"7313","DOI":"10.1002\/anie.201901724","article-title":"Regioselective functionalization of 7-azaindole by controlled annular isomerism: The directed metalation-group dance","volume":"58","author":"Dalziel","year":"2019","journal-title":"Angew. Chem., Int. Ed."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"3092","DOI":"10.1021\/ja0702770","article-title":"Intramolecular C\u2013H activation directed self-assembly of an organoplatinum(II) molecular square","volume":"129","author":"Zhao","year":"2007","journal-title":"J. Am. Chem. Soc."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"4730","DOI":"10.1016\/j.bmcl.2017.08.069","article-title":"Discovery of N-substituted 7-azaindoles as PIM1 kinase inhibitors\u2014Part I","volume":"27","author":"Barberis","year":"2017","journal-title":"Bioorg. Med. Chem. Lett."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1021\/jo7020345","article-title":"Deprotonative metalation of five-membered aromatic heterocycles using mixed lithium-zinc species","volume":"73","author":"Seggio","year":"2008","journal-title":"J. Org. Chem."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"10280","DOI":"10.1002\/chem.200901432","article-title":"Deprotonative metalation of functionalized aromatics using mixed lithium-cadmium, lithium-indium, and lithium-zinc species","volume":"15","author":"Nguyen","year":"2009","journal-title":"Chem. Eur. J."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"13498","DOI":"10.1021\/acs.joc.8b02397","article-title":"Deprotonative metalation of methoxy-substituted arenes using lithium 2,2,6,6-tetramethylpiperidide: Experimental and computational study","volume":"83","author":"Akimoto","year":"2018","journal-title":"J. Org. Chem."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"9668","DOI":"10.1002\/anie.201104297","article-title":"\u201cLiZn(TMP)3\u201d, a zincate or a turbo-lithium amide reagent? Dosy NMR spectroscopic evidence","volume":"50","author":"Mulvey","year":"2011","journal-title":"Angew. Chem. Int. Ed."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"3615","DOI":"10.1055\/s-0036-1591953","article-title":"In situ \u2018trans-metal trapping\u2019: An efficient way to extend the scope of aromatic deprotometalation","volume":"50","author":"Erb","year":"2018","journal-title":"Synthesis"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"1475","DOI":"10.3762\/bjoc.11.160","article-title":"Deproto-metalation of N-arylated pyrroles and indoles using a mixed lithium-zinc base and regioselectivity-computed CH acidity relationship","volume":"11","author":"Hedidi","year":"2015","journal-title":"Beilstein J. Org. Chem."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"13284","DOI":"10.1002\/chem.201101993","article-title":"Deprotonative metalation of chloro- and bromopyridines using amido-based bimetallic species and regioselectivity-computed CH acidity relationships","volume":"17","author":"Nguyen","year":"2011","journal-title":"Chem. Eur. J."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"3505","DOI":"10.1139\/v85-574","article-title":"Acidity measurements in THF. V. Heteroaromatic compounds containing 5-membered rings","volume":"63","author":"Fraser","year":"1985","journal-title":"Can. J. Chem."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"1475","DOI":"10.1039\/c3ob42380h","article-title":"Deproto-metallation using a mixed lithium-zinc base and computed CH acidity of 1-aryl 1H-benzotriazoles and 1-aryl 1H-indazoles","volume":"12","author":"Nagaradja","year":"2014","journal-title":"Org. Biomol. Chem."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"2243","DOI":"10.1021\/jo026559u","article-title":"Lithiation of 2-chloro- and 2-methoxypyridine with lithium dialkylamides: Initial ortho-direction or subsequent lithium ortho-stabilization?","volume":"68","author":"Gros","year":"2003","journal-title":"J. Org. Chem."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"4671","DOI":"10.1039\/c1ob05267e","article-title":"N-aryl pyrazoles: DFT calculations of CH acidity and deprotonative metallation using a combination of lithium and zinc amides","volume":"9","author":"Chevallier","year":"2011","journal-title":"Org. Biomol. Chem."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"2478","DOI":"10.1021\/acs.chemrev.5b00484","article-title":"The halogen bond","volume":"116","author":"Cavallo","year":"2016","journal-title":"Chem. Rev."},{"key":"ref_59","first-page":"184","article-title":"Synthesis of heterobiaryls featuring 1,4 N\u2026S inter-ring interactions","volume":"48","author":"Tilly","year":"2016","journal-title":"Synthesis"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"3139","DOI":"10.1039\/c1ob05310h","article-title":"Rapid synthesis of bis(hetero)aryls by one-pot Masuda borylation-suzuki coupling sequence and its application to concise total syntheses of meridianins A and G","volume":"9","author":"Merkul","year":"2011","journal-title":"Org. Biomol. Chem."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"6454","DOI":"10.1016\/j.bmcl.2012.08.053","article-title":"Discovery of 1H-pyrrolo[2,3-c]pyridine-7-carboxamides as novel, allosteric mGluR5 antagonists","volume":"22","author":"Koller","year":"2012","journal-title":"Bioorg. Med. Chem. Lett."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"5337","DOI":"10.1021\/jm3002982","article-title":"Design, synthesis, and evaluation of 3,5-disubstituted 7-azaindoles as Trk inhibitors with anticancer and antiangiogenic activities","volume":"55","author":"Hong","year":"2012","journal-title":"J. Med. Chem."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"5718","DOI":"10.1021\/ol4027478","article-title":"Direct C-2 arylation of 7-azaindoles: Chemoselective access to multiarylated derivatives","volume":"15","author":"Kannaboina","year":"2013","journal-title":"Org. Lett."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"14015","DOI":"10.1021\/acs.joc.9b02187","article-title":"Pd-catalyzed sequential arylation of 7-azaindoles: Aggregate-induced emission of tetra-aryl 7-azaindoles","volume":"84","author":"Cardoza","year":"2019","journal-title":"J. Org. Chem."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"131337","DOI":"10.1016\/j.tet.2020.131337","article-title":"Cu(II)-catalyzed sulfonylation of 7-azaindoles using DABSO as SO2-source and its mechanistic study","volume":"76","author":"Dar","year":"2020","journal-title":"Tetrahedron"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"5294","DOI":"10.1021\/ol502447w","article-title":"Rhodium-catalyzed regioselective C-H chlorination of 7-azaindoles using 1,2-dichloroethane","volume":"16","author":"Qian","year":"2014","journal-title":"Org. Lett."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"644","DOI":"10.1007\/s11172-016-1349-4","article-title":"Quantum chemical study of regioselectivity of reactions of substituted pyrido[1,2-a]benzimidazoles with electrophiles","volume":"65","author":"Begunov","year":"2016","journal-title":"Russ. Chem. Bull."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"2756","DOI":"10.1002\/ejoc.202100362","article-title":"Thiazolo[5,4-f]quinoxalines, oxazolo[5,4-f]quinoxalines and pyrazino[b,e]isatins: Synthesis from 6-aminoquinoxalines and properties","volume":"2021","author":"Lassagne","year":"2021","journal-title":"Eur. J. Org. Chem."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"1433","DOI":"10.1063\/1.1740412","article-title":"Molecular-orbital theory of orientation in aromatic, heteroaromatic, and other conjugated molecules","volume":"22","author":"Fukui","year":"1954","journal-title":"J. Chem. Phys."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"13256","DOI":"10.1021\/jp803813e","article-title":"H\u00fcckel-Lewis projection method: A \u201cweights watcher\u201d for mesomeric structures","volume":"112","author":"Carissan","year":"2008","journal-title":"J. Phys. Chem. A"},{"key":"ref_71","unstructured":"Carissan, Y., Hagebaum-Reignier, D., Goudard, N., and Humbel, S. (2021, March 25). HuLiS Program: Lewis-Embedded in H\u00fcckel Theory. Available online: http:\/\/www.hulis.free.fr."},{"key":"ref_72","first-page":"36","article-title":"Weight Watchers \u00e9lectronique: Calculez votre poids de formes r\u00e9sonantes","volume":"406","author":"Carissan","year":"2016","journal-title":"L\u2019Act. Chim."},{"key":"ref_73","unstructured":"Goudard, N., Carissan, Y., Hagebaum-Reignier, D., and Humbel, S. (2021, March 23). HuLiS 3.3.4. Available online: http:\/\/ism2.univ-amu.fr\/hulis."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"8761","DOI":"10.1016\/j.tet.2007.06.037","article-title":"(N-7-Azaindolyl)oligothiophenes: Synthesis, characterization, and photophysical properties","volume":"63","author":"Hong","year":"2007","journal-title":"Tetrahedron"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"3498","DOI":"10.1016\/j.bmc.2014.04.028","article-title":"Synthesis of C,N\u2032-linked bis-heterocycles using a deprotometalation-iodination-N-arylation sequence and evaluation of their antiproliferative activity in melanoma cells","volume":"22","author":"Hedidi","year":"2014","journal-title":"Bioorg. Med. Chem."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"6467","DOI":"10.1016\/j.tet.2016.08.056","article-title":"Synthesis of N-pyridyl azoles using a deprotometalation-iodolysis-N-arylation sequence and evaluation of their antiproliferative activity in melanoma cells","volume":"72","author":"Hedidi","year":"2016","journal-title":"Tetrahedron"},{"key":"ref_77","first-page":"4500","article-title":"Synthesis of N-aryl and N-heteroaryl \u03b3-, \u03b4-, and \u03b5-lactams using deprotometalation-iodination and N-arylation, and properties thereof","volume":"49","author":"Amara","year":"2017","journal-title":"Synthesis"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"5903","DOI":"10.1002\/ejoc.201701004","article-title":"Fused systems based on 2-aminopyrimidines: Synthesis combining deprotolithiation-in situ zincation with N-arylation reactions and biological properties","volume":"2017","author":"Hedidi","year":"2017","journal-title":"Eur. J. Org. Chem."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"5302","DOI":"10.1002\/ejoc.201900352","article-title":"Conversion of isatins to tryptanthrins, heterocycles endowed with a myriad of bioactivities","volume":"2019","author":"Amara","year":"2019","journal-title":"Eur. J. Org. Chem."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"7512","DOI":"10.1021\/jo971176v","article-title":"NMR chemical shifts of common laboratory solvents as trace impurities","volume":"62","author":"Gottlieb","year":"1997","journal-title":"J. Org. Chem."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"4133","DOI":"10.1021\/jo00252a055","article-title":"Regiospecific 1,4-addition with Grignard-derived mixed triorganozincate reagents","volume":"53","author":"Kjonaas","year":"1988","journal-title":"J. Org. Chem."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1107\/S0021889898007717","article-title":"SIR97: A new tool for crystal structure determination and refinement","volume":"32","author":"Altomare","year":"1999","journal-title":"J. Appl. Crystallogr."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"112","DOI":"10.1107\/S0108767307043930","article-title":"A short history of SHELX","volume":"64","author":"Sheldrick","year":"2008","journal-title":"Acta Crystallogr. Sect. A Found. Crystallogr."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"849","DOI":"10.1107\/S0021889812029111","article-title":"WinGX and ORTEP for windows: An update","volume":"45","author":"Farrugia","year":"2012","journal-title":"J. Appl. Crystallogr."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1107\/S2053273314026370","article-title":"SHELXT\u2014Integrated space-group and crystal-structure determination","volume":"71","author":"Sheldrick","year":"2015","journal-title":"Acta Crystallogr. Sect. A Found. Crystallogr."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1107\/S2053229614024218","article-title":"Crystal structure refinement with shelxl","volume":"71","author":"Sheldrick","year":"2015","journal-title":"Acta Crystallogr. Sect. C Struct. Chem."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"565","DOI":"10.1107\/S0021889897003117","article-title":"ORTEP-3 for windows\u2014A version of ORTEP-III with a graphical user interface (GUI)","volume":"30","author":"Farrugia","year":"1997","journal-title":"J. Appl. Crystallogr."},{"key":"ref_88","unstructured":"Frisch, M.J., Trucks, G.W., Schlegel, H.B., Scuseria, G.E., Robb, M.A., Cheeseman, J.R., Scalmani, G., Barone, V., Mennucci, B., and Petersson, G.A. (2009). Gaussian 09, Gaussian Inc.. Revision A.02."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"3032","DOI":"10.1063\/1.474659","article-title":"A new integral equation formalism for the polarizable continuum model: Theoretical background and applications to isotropic and anisotropic dielectrics","volume":"107","author":"Cances","year":"1997","journal-title":"J. Chem. Phys."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"8940","DOI":"10.1016\/j.tet.2009.08.046","article-title":"Palladium-catalyzed tandem alkenyl- and aryl-C-N bond formation: A cascade N-annulation route to 1-functionalized 7-azaindoles","volume":"65","author":"Hodgkinson","year":"2009","journal-title":"Tetrahedron"},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"7293","DOI":"10.1016\/j.tetlet.2009.10.041","article-title":"Copper-catalyzed C-N coupling of amides and nitrogen-containing heterocycles in the presence of cesium fluoride","volume":"50","author":"Phillips","year":"2009","journal-title":"Tetrahedron Lett."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"3140","DOI":"10.1016\/j.tetlet.2016.06.019","article-title":"N-arylation of nitrogen containing heterocycles with aryl halides using copper nanoparticle catalytic system","volume":"57","author":"Pai","year":"2016","journal-title":"Tetrahedron Lett."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"7727","DOI":"10.1021\/ja016226z","article-title":"A general and efficient copper catalyst for the amidation of aryl halides and the N-arylation of nitrogen heterocycles","volume":"123","author":"Klapars","year":"2001","journal-title":"J. Am. Chem. Soc."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"7171","DOI":"10.1016\/j.tetlet.2011.10.128","article-title":"A manganese\/copper bimetallic catalyst for C\u2013N coupling reactions under mild conditions in water","volume":"52","author":"Teo","year":"2011","journal-title":"Tetrahedron Lett."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"5248","DOI":"10.1021\/ic000465q","article-title":"Blue-luminescent\/electroluminescent Zn(II) compounds of 7-azaindole and N-(2-pyridyl)-7-azaindole: Zn(7-azaindole)2(CH3COO)2, Zn(NPA)(CH3COO)2, and Zn(NPA)((S)-(+)-CH3CH2CH(CH3)COO)2 (NPA = N-(2-pyridyl)-7-azaindole)","volume":"39","author":"Wu","year":"2000","journal-title":"Inorg. Chem."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"1665","DOI":"10.1016\/j.jorganchem.2004.02.023","article-title":"Synthesis of Re(I) complexes bearing tridentate 2,6-bis(7\u2032-azaindolyl)phenyl ligand with green emission properties","volume":"689","author":"Tani","year":"2004","journal-title":"J. Organomet. Chem."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"910","DOI":"10.1166\/jnn.2016.10748","article-title":"Novel organic semiconductors based on phenyl and phenylthienyl derivatives for organic thin-film transistors","volume":"16","author":"Lee","year":"2016","journal-title":"J. Nanosci. Nanotechnol."}],"container-title":["Molecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1420-3049\/26\/20\/6314\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T07:18:14Z","timestamp":1760167094000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1420-3049\/26\/20\/6314"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,10,19]]},"references-count":97,"journal-issue":{"issue":"20","published-online":{"date-parts":[[2021,10]]}},"alternative-id":["molecules26206314"],"URL":"https:\/\/doi.org\/10.3390\/molecules26206314","relation":{},"ISSN":["1420-3049"],"issn-type":[{"type":"electronic","value":"1420-3049"}],"subject":[],"published":{"date-parts":[[2021,10,19]]}}}