4-甲氧基吲哚-3-乙腈

反应条件: temp:60.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To a solution of sodium methanolate (261 mg, 4.8 mmol, 1.5 eq.) in anhydrous ethanol (40 mL) were added, under an argon atmosphere, of (4-methoxy-1H-indol-3-yl)-acetonitrile (600 mg, 3.2 mmol, 1.0 eq.) and, after 30 minutes stirring, pyridine-3-carbaldehyde (908 μL, 9.7 mmol, 3.0 eq.). The reaction apparatus was protected from light and the mixture heated at 60° C. Several amounts of sodium methanolate (4×1.0 eq.) and pyridine-3-carbaldehyde (4×1.0 eq.) were added after stirring for 24, 48, 72 and 96 hours respectively. The reaction was pursued for 2 days (6 days overall) at 60° C. and then, the solvent was removed under reduced pressure and the crude taken up in ethyl acetate. The organic layer was washed with water and brine, dried over MgSO4 and then, evaporated. The residue was purified by silica gel flash-column chromatography (eluent: CH2Cl2/EtOH, 98:2 to 97:3) to afford, after trituration with diethyl ether, the compound (27) as a yellow powder (510 mg, 58%). TLC: Rf=0.30 (CH2Cl2 96/EtOH 4); mp: 177° C.; 1H NMR (DMSO, 500 MHz): δ (ppm): 3.90 (3H, s, 4′-methoxy), 6.66 (1H, d, J5′-6′=7.9 Hz, H5′), 7.07 (1H, d, J7′-6′=7.9 Hz, H7′), 7.14 (1H, t, J6′-5′=J6′-7′=7.9 Hz, H6′), 7.55 (1H, dd, J5″-4″=7.9 Hz, J5″-6″=4.9 Hz, H5″), 7.62 (1H, s, H2′), 7.78 (1H, s, H3), 8.31 (1H, d, J4″-5″=7.9 Hz, H4″), 8.59 (1H, d, J6″-5″=4.9 Hz, H6″), 8.91 (1H, s, H2″), 11.67 (1H, s, indolic H); 13C NMR (DMSO, 75.5 MHz): δ (ppm): 55.6 (4′-methoxy), 101.4 (C5′), 106.0 (C7′), 108.6 (C2), 111.9 (C3′), 114.7 (C3a′), 119.1 (C1), 124.1 (C5″), 124.3 (C6′), 126.6 (C2′), 131.1 (C3″), 134.9 (C4″), 138.0 (C3), 139.0 (C7a′), 150.3 (C6″), 150.4 (C2″), 153.7 (C4′); ESI-MS: m/z 276.1 ([M+H]+), 298.1 ([M+Na]+); HRESI-MS: m/z 276.1137 (calcd for C17H14N3O, 276.1137). after stirring for 24, 48, 72 and 96 hours respectively (6 days overall) at 60° C. and then, the solvent was removed under reduced pressure The organic layer was washed with water and brine dried over MgSO4 evaporated The residue was purified by silica gel flash-column chromatography (eluent: CH2Cl2/EtOH, 98:2 to 97:3) to afford

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To a solution of 4-methoxyindole (1.0 g, 6.8 mmol, 1.0 eq.) in a mixture of acetic acid (2 mL) and water (1 mL) were added, at 0° C., formaldehyde (720 μL, 37% in H2O, 8.9 mmol, 1.3 eq) and dimethylamine (1.23 mL, 40% in H2O, 10.9 mmol, 1.6 eq). The mixture was stirred at room temperature for 6 hours and then, quenched with ice and 5 M aqueous sodium hydroxide. The mixture was extracted with dichloromethane and then, the organic layer was dried over MgSO4 and partially evaporated. To the solution gramine in dichloromethane (20 mL) were added, under an argon atmosphere, anhydrous toluene (40 mL) and methyl iodide (845 μL, 13.6 mmol, 2.0 eq.). The mixture was stirred at room temperature for 12 hours and then, concentrated under reduced pressure. To the residue taken up in anhydrous THF (60 mL) were added, under an argon atmosphere, TMSCN (1.28 mL, 10.2 mmol, 1.5 eq.) and TBAF (20.4 mL, 1M, 20.4 mmol, 3.0 eq.). The mixture was stirred at room temperature for 4 hours and then, concentrated under reduced pressure. The crude was taken up in ethyl acetate and the organic layer was washed with aqueous bicarbonate solution and then dried over MgSO4. The solvent was removed under reduced pressure, and the residue purified by silica gel pad filtration (eluent: EtOAc) to afford (4-methoxy-1H-indol-3-yl)-acetonitrile as a beige solid (0.80 g, 68%). were added, at 0° C. quenched with ice and 5 M aqueous sodium hydroxide The mixture was extracted with dichloromethane the organic layer was dried over MgSO4 partially evaporated To the solution gramine in dichloromethane (20 mL) were added, under an argon atmosphere The mixture was stirred at room temperature for 12 hours concentrated under reduced pressure were added, under an argon atmosphere The mixture was stirred at room temperature for 4 hours concentrated under reduced pressure the organic layer was washed with aqueous bicarbonate solution dried over MgSO4 The solvent was removed under reduced pressure the residue purified by silica gel pad filtration (eluent: EtOAc)

反应条件: temp:60.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To a solution of sodium methanolate (261 mg, 4.8 mmol, 1.5 eq.) in anhydrous ethanol (40 mL) were added, under an argon atmosphere, of (4-methoxy-1H-indol-3-yl)-acetonitrile (600 mg, 3.2 mmol, 1.0 eq.) and, after 30 minutes stirring, pyridine-3-carbaldehyde (908 μL, 9.7 mmol, 3.0 eq.). The reaction apparatus was protected from light and the mixture heated at 60° C. Several amounts of sodium methanolate (4×1.0 eq.) and pyridine-3-carbaldehyde (4×1.0 eq.) were added after stirring for 24, 48, 72 and 96 hours respectively. The reaction was pursued for 2 days (6 days overall) at 60° C. and then, the solvent was removed under reduced pressure and the crude taken up in ethyl acetate. The organic layer was washed with water and brine, dried over MgSO4 and then, evaporated. The residue was purified by silica gel flash-column chromatography (eluent: CH2Cl2/EtOH, 98:2 to 97:3) to afford, after trituration with diethyl ether, the compound (27) as a yellow powder (510 mg, 58%). TLC: Rf=0.30 (CH2Cl2 96/EtOH, 4); mp: 177° C.; 1H NMR (DMSO, 500 MHz): δ (ppm): 3.90 (3H, s, 4′-methoxy), 6.66 (1H, d, J5′-6′=7.9 Hz, H5′), 7.07 (1H, d, J7′-6′=7.9 Hz, H7′), 7.14 (1H, t, J6′-5′=J6′-7′=7.9 Hz, H6′), 7.55 (1H, dd, J5″-4″=7.9 Hz, J5″-6″=4.9 Hz, H5″), 7.62 (1H, s, H2′), 7.78 (1H, s, H3), 8.31 (1H, d, J4″-5″=7.9 Hz, H4″), 8.59 (1H, d, J6″-5″=4.9 Hz, H6″), 8.91 (1H, s, H2″), 11.67 (1H, s, indolic H); 13C NMR (DMSO, 75.5 MHz): δ (ppm): 55.6 (4′-methoxy), 101.4 (C5′), 106.0 (C7′), 108.6 (C2), 111.9 (C3′), 114.7 (C3a′), 119.1 (C1), 124.1 (C5″), 124.3 (C6′), 126.6 (C2′), 131.1 (C3″), 134.9 (C4″), 138.0 (C3), 139.0 (C7a′), 150.3 (C6″), 150.4 (C2″), 153.7 (C4′); ESI-MS: m/z 276.1 ([M+H]+), 298.1 ([M+Na]+); HRESI-MS: m/z 276.1137 (calcd for C17H14N3O, 276.1137). after stirring for 24, 48, 72 and 96 hours respectively (6 days overall) at 60° C. and then, the solvent was removed under reduced pressure The organic layer was washed with water and brine dried over MgSO4 evaporated The residue was purified by silica gel flash-column chromatography (eluent: CH2Cl2/EtOH, 98:2 to 97:3) to afford

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To a solution of 4-methoxyindole (1.0 g, 6.8 mmol, 1.0 eq.) in a mixture of acetic acid (2 mL) and water (1 mL) were added, at 0° C., formaldehyde (720 μL, 37% in H2O, 8.9 mmol, 1.3 eq) and dimethylamine (1.23 mL, 40% in H2O, 10.9 mmol, 1.6 eq). The mixture was stirred at room temperature for 6 hours and then, quenched with ice and 5 M aqueous sodium hydroxide. The mixture was extracted with dichloromethane and then, the organic layer was dried over MgSO4 and partially evaporated. To the solution gramine in dichloromethane (20 mL) were added, under an argon atmosphere, anhydrous toluene (40 mL) and methyl iodide (845 μL, 13.6 mmol, 2.0 eq.). The mixture was stirred at room temperature for 12 hours and then, concentrated under reduced pressure. To the residue taken up in anhydrous THF (60 mL) were added, under an argon atmosphere, TMSCN (1.28 mL, 10.2 mmol, 1.5 eq.) and TBAF (20.4 mL, 1M, 20.4 mmol, 3.0 eq.). The mixture was stirred at room temperature for 4 hours and then, concentrated under reduced pressure. The crude was taken up in ethyl acetate and the organic layer was washed with aqueous bicarbonate solution and then dried over MgSO4. The solvent was removed under reduced pressure, and the residue purified by silica gel pad filtration (eluent: EtOAc) to afford (4-methoxy-1H-indol-3-yl)-acetonitrile as a beige solid (0.80 g, 68%). were added, at 0° C. quenched with ice and 5 M aqueous sodium hydroxide The mixture was extracted with dichloromethane the organic layer was dried over MgSO4 partially evaporated To the solution gramine in dichloromethane (20 mL) were added, under an argon atmosphere The mixture was stirred at room temperature for 12 hours concentrated under reduced pressure were added, under an argon atmosphere The mixture was stirred at room temperature for 4 hours concentrated under reduced pressure the organic layer was washed with aqueous bicarbonate solution dried over MgSO4 The solvent was removed under reduced pressure the residue purified by silica gel pad filtration (eluent: EtOAc)