Synlett, Table of Contents Synlett 2022; 33(08): 791-794DOI: 10.1055/a-1774-7618 letter A Sydnone-Based Route to Indazolo[2,3-a]quinoxaline Derivatives Authors Manon Louis‡ Alex Talbot‡ Diana Lamaa Antoine Sallustrau Davide Audisio Frédéric Taran ∗ Recommend Article Abstract Buy Article(opens in new window) All articles of this category(opens in new window) Abstract A new synthetic route to indazolo[2,3-a]quinoxaline derivatives is described. The strategy is based on the 1,3-dipolar cycloaddition of arynes to quinoxaline–sydnone derivatives as a key step. The polyaromatic sydnones were prepared through a copper-promoted intramolecular cyclization of the C-4 position of sydnones on imines. Key words Key wordssydnones - cycloaddition - quinoxalines - indazoloquinoxalines Full Text References References and Notes See for example: 1a Kalinin AA, Mamedov VA. Chem. Heterocycl. Compd. 2011; 46: 1423 1b Mamedov VA, Kalinin AA. Chem. Heterocycl. Compd. 2010; 46: 641 2a Moarbess G, Deleuze-Masquefa C, Bonnard V, Gayraud-Paniagua S, Vidal J.-R, Bressolle F, Pinguet F, Bonnet P.-A. Bioorg. Med. Chem. 2008; 16: 6601 2b Patinote C, Karroum NB, Moarbess G, Deleuze-Masquef C, Hadj-Kaddour K, Cuq P, Diab-Assaf M, Kassab I, Bonnet P.-A. Eur. J. Med. Chem. 2017; 138: 909 3a Sengupta SK. In Cancer Chemotherapeutic Agents . Foye WO. American Chemical Society; Washington: 1995: 205 3b Koścień E, Gondek E, Pokladko M, Jarosz B, Vlokh R, Kityk AV. Mater. Chem. Phys. 2009; 114: 860 4 Murugan A, Vidyacharan S, Ghosh R, Sharada DS. ChemistrySelect 2017; 2: 3511 5 Vidyacharan S, Murugan A, Sharada DS. J. Org. Chem. 2016; 81: 2837 6 Vidyacharan S, Sagar A, Chaitra NC, Sharada DS. RSC Adv. 2014; 4: 34232 7 He Z, Bae M, Wu J, Jamison TF. Angew. Chem. Int. Ed. 2014; 53: 14451 8a Yen-Pon E, Champagne PA, Plougastel L, Gabillet S, Thuéry P, Johnson M, Muller G, Pieters G, Taran F, Houk K, Audisio D. J. Am. Chem. Soc. 2019; 141: 1435 8b Plougastel L, Lamaa D, Yen-Pon E, Audisio D, Taran F. Tetrahedron 2020; 76: 131250 8c Yen-Pon E, Buttard F., Frédéric L., Thuéry P, Taran F, Pieters G, Champagne PA, Audisio D. JACS Au 2021; 1: 807 9a Yang Y, Gong H, Kuang C. Synthesis 2013; 45: 1469 9b Brown AW, Harrity JP. A. J. Org. Chem. 2015; 80: 2467 10 Yang Y, Kuang C. Eur. J. Org. Chem. 2014; 7810 11 Browne DL, Harrity JP. A. Tetrahedron 2010; 66: 553 12 Burson WC. III, Jones DR, Turnbull K, Preston PN. Synthesis 1991; 745 13 Comas-Barceló J, Foster RS, Fiser B, Gomez-Bengoa E, Harrity JP. A. Chem. Eur. J. 2015; 21: 3257 For reviews, see: 14a Porte K, Riomet M, Figliola C, Audisio D, Taran F. Chem. Rev. 2021; 121: 6718 14b Comas-Barceló J, Harrity JP. A. Synthesis 2017; 49: 1168 14c Hladíková V, Váňa J, Hanusek J. Beilstein J. Org. Chem. 2018; 14: 1317 15a Wallace S, Chin JW. Chem. Sci. 2014; 5: 1742 15b Plougastel L, Koniev O, Specklin S, Decuypere E, Créminon C, Buisson D.-A, Wagner A, Kolodych S, Taran F. Chem. Commun. 2014; 50: 9376 15c Narayanam MK, Liang Y, Houk KN, Murphy JM. Chem. Sci. 2016; 7: 1257 16a Wu C, Fang Y, Larock RC, Shi F. Org. Lett. 2010; 12: 2234 16b Fang Y, Wu C, Larock RC, Shi F. J. Org. Chem. 2011; 76: 8840 17 Shi J, Li L, Li Y. Chem. Rev. 2021; 121: 3892 18 4-[4-(Methoxycarbonyl)phenyl][1,2,3]oxadiazolo[3,4-a]quinoxalin-10-ium-3-olate; Typical Procedure PPhMe2 (15.6 μL, 0.11 mmol, 1.1 equiv) and methyl 4-formylbenzoate (32.9 mg, 0.2 mmol, 2 equiv) were added to a solution of 1a (20 mg, 0.10 mmol, 1 equiv) in anhydrous MeCN (0.5 mL). After 6 h CuOTf2 (72.3 mg, 0.2 mmol, 2 equiv) was added and the mixture was stirred for an additional hour. The solvent was evaporated to give a crude product that was triturated in MeOH then isolated by centrifugation to afford the clean product as a white powder; yield: 26.0 mg (0.081 mmol, 81%); mp = 228 °C. IR (neat): 1770, 1759, 1723, 1577, 1497, 1436, 1302, 1121, 1107, 964, 883, 764, 707, 730 cm–1. 1H NMR (400 MHz, DMSO-d 6): δ = 8.45 (dd, J = 8.4, 1.0 Hz, 1 H), 8.18 (dd, J = 8.3, 0.9 Hz, 1 H), 8.16–8.10 (m, 4 H), 8.04 (ddd, J = 8.4, 7.3, 1.3 Hz, 1 H), 7.89 (ddd, J = 8.5, 7.3, 1.3 Hz, 1 H), 3.92 (s, 3 H). 13C NMR (101 MHz, DMSO-d 6): δ = 165.8, 162.9, 153.0, 140.3, 138.0, 133.5, 131.4, 130.2, 130.0, 129.8 (2 C), 128.9 (2 C), 121.6, 115.8, 103.1, 52.4. LCMS (ESI): m/z 322.3 [M + H]+. HRMS (ESI): m/z [M + H]+calcd for C17H12N3O4: 322.0828; found: 322.0831. Methyl 4-(Indazolo[2,3-a]quinoxalin-6-yl)benzoate (5a); Typical Procedure TBAF (1 M in THF, 0.093 mL, 0.093 mmol, 1.5 equiv) was added dropwise over 5 min to a solution of 4a (20 mg, 0.06 mmol, 1 equiv) and the aryne precursor 2-(trimethylsilyl)phenyl triflate (27.9 mg, 0.093 mmol, 1.5 equiv) in anhydrous THF (400 µL). To drive the reaction to completion, additional 2-(trimethylsilyl)phenyl triflate (0.093 mmol, 1.5 equiv) and TBAF (0.093 mmol, 1.5 equiv) were successively added every hour for 4 h. The mixture was then evaporated and purified by column chromatography [silica gel, heptane–EtOAc (80:20)] to give a grey solid; yield: 9.7 mg (0.028 mmol, 46%). IR (neat): 2963, 2876, 1723, 1474, 1263, 1152, 1031, 883, 759, 638 cm–1. 1H NMR (400 MHz, CDCl3): δ = 8.90 (dd, J = 8.2, 1.2 Hz, 1 H), 8.37–8.30 (m, 2 H), 8.27 (dd, J = 8.1, 1.2 Hz, 1 H), 8.08 (d, J = 8.6 Hz, 1 H), 8.05–7.99 (m, 2 H), 7.88–7.73 (m, 2 H), 7.62–7.52 (m, 2 H), 7.25–7.19 (m, 1 H), 4.02 (s, 3 H). 13C NMR (101 MHz, CDCl3): δ = 166.8, 153.2, 149.5, 142.2, 138.2, 131.9, 130.3 (2 C), 130.2, 129.7, 129.2 (2 C), 128.5, 128.4, 128.1, 125.7, 123.6, 121.1, 117.8, 117.2, 116.7, 52.6. LCMS (ESI): m/z 354.8 [M + H]+. HRMS (ESI): m/z [M + H]+ calcd for C22H16N3O2: 354.1242; found: 354.1248. Supplementary Material Supplementary Material Supporting Information (PDF) (opens in new window)
