A Sydnone-Based Route to Indazolo[2,3-a]quinoxaline Derivatives

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

sydnones - cycloaddition - quinoxalines - indazoloquinoxalines

Publication History

Received: 28 January 2022

Accepted after revision: 17 February 2022

Accepted Manuscript online:
17 February 2022

Article published online:
25 April 2022

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• 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.