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With triethylamine; In acetonitrile; for 0.5h;Microwave irradiation; |
General procedure: IL-supported compound 1 (1 g) was added to a 50 ml flask with 0.11 g of <strong>[5580-79-0]TFNB</strong> 2 (3 equiv, 0.59 mmol) and TEA 0.16 mL (6 equiv, 1.15 mmol) in 10 ml acetonitrile. The reaction mixture was heated for 30 min under microwave in open vessel condition. After the completion of reaction, ether was added to the reaction mixture to precipitate the two isomers of the IL-supported compounds 3 and 4 and washed with ether (30 mL × 2). IL-supported compounds 3 and 4 dissolved in acetonitrile (10 mL), piperazine or homopiperazine or aminomethylpiperidine (3 equiv, 0.57 mmol), and 0.18 ml TEA (6 equiv, 1.18 mmol) were stirred atroomtemperaturefor 8 h, then ether was added to the reaction mixture to precipitate the IL-supported compounds 5 and 6. IL-supported compounds 5 and 6 dissolved in acetonitrile (10 mL) with 0.20 g of N,N?ditertbutoxycarbonyl-1Hbenzotriazole-1-carbox-amidine 7 (3 equiv, 0.56 mmol) and 0.16 ml TEA (6 equiv, 1.15 mmol) were stirred at room temperature for 18 h. The ether (50 mL) was added after the reaction was completed. The precipitation was filtered, and dried under high vacuum to give guanidinyl compounds 8 and 9. IL-supported compounds 8 and 9 dissolved in methanol (10 mL) with 233 mg of powder Zn and 112 mg of NH4COOH (10 equiv, 1.79 mmol) were stirred at room temperature for 1 h. Monitoring the reaction progress by TLC showed that compound 10 was released from ionic liquid support. The filtrate was concentrated after precipitation, dried well and submitted to spectrum analysis. Further purification by column chromatography furnished the pure guanidinyl heterocyclic linked quinaxolinones 10 as a liquid. Compound 10a: 1H NMR (300 MHz, CDCl3) delta 10.18 (s, -NH), 8.95 (s, 1H), 7.39-7.35 (m, 2H), 7.32-7.30 (m, 1H), 7.20-7.17 (m, 2H), 6.40 (d, J = 11.2 Hz, 1H), 4.05-3.91 (m, 2H), 3.71 (m, 4H), 3.19 (m, 4H), 2.86-2.78 (dd, J = 13.3, 10.8 Hz, 1H), 1.50 (s, 18H); 13C NMR(75 MHz, CDCl3) delta 168.5, 164.7, 160.4, 159.2, 155.9, 152.8, 149.3, 136.1, 135.9, 129.2, 128.9, 128.6, 127.1, 126.7, 120.2, 118.0, 99.9, 97.8, 50.8, 44.5, 39.9, 31.1, 29.6, 28.0; IR (cm-1, neat): 3275, 2924, 2852, 1678; MS (ESI-MS) m/z: 601 [M+H] +; HRMS Calcd for C30H38F2N6O5: m/z 600.2872; Found 601.2948 [M+H] +. The IL-supported compound 11wascleaved in methanol (10 mL) and 26 mg KCN (3 equiv, 0.40 mmol) for 18 h. Ether (50 mL) was added to precipitateIL-1 and the filtrate was concentrated to give compounds 12 as a liquid. Compound 12a: 1H NMR (300 MHz, CDCl3) delta 7.31-7.22 (m, 3H), 7.17-7.15 (m, 2H), 6.25-6.20 (dd, J = 12.3, 2.0 Hz, 1H), 4.31 (t, J = 6.1 Hz, 1H), 3.63 (s, 3H), 3.38-3.20 (m, 4H), 3.07 (d, J = 6.5 Hz, 2H), 2.81-2.76 (m, 4H), 1.50 (s, 18H); 13C NMR (75 MHz, CDCl3) delta 173.7, 167.7, 148.9, 145.6, 143.8, 142.6, 136.4, 132.4, 128.7, 128.4, 126.8, 114.8, 114.5, 110.2, 97.5, 83.3, 52.8, 51.8, 49.9, 46.2, 38.6; IR (cm-1, neat): 2871, 1737; MS (ESI-MS) m/z: 633 [M+H+]; HRMS Calcd for C31H42F2N6O6: m/z 632.3134; Found 633.3211 [M+H+]. |
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