Reaction Steps
To a solution of tert-butyl 3-(cyanomethyl)-5-methoxy-1H-indol-1-carboxylate (719 mg, 2.51 mmol, 1.0 eq.) in anhydrous THF (30 mL) was added, under an argon atmosphere, NaH (106 mg, 80%, 3.52 mmol, 1.4 eq.). The mixture was stirred at room temperature for 2 hours, and then cooled to 0° C. before the addition of 2-fluoro-pyridine-3-carbaldehyde (440 mg, 3.52 mmol, 1.4 eq.) in anhydrous THF (6 mL). The reaction apparatus was protected from light and the mixture was stirred at 0° C. for 24 hours, at room temperature for 24 hours too and then, quenched with a saturated aqueous ammonium chloride solution. The mixture was stirred again at room temperature for 24 hours and extracted with ethyl acetate. The organic layer was washed with brine and dried over MgSO4. The solvent was removed under reduced pressure, and the residue purified by silica gel flash-column chromatography (eluent: CH2Cl2/EtOH, 98/2) to afford, after trituration with diethyl ether, the compound (48) as a yellow powder (220 mg, 30%). IR νmax (cm−1): 2219 (νCN), 3228 (νN—H); 1H NMR (DMSO, 300 MHz): δ (ppm): 3.81 (3H, s, 5′-methoxy), 6.91 (1H, dd, J6′-7′=8.9 Hz, J6′-4′=2.1 Hz, H6′), 7.42 (1H, d, J7′-6′=8.9 Hz, H7′), 7.43 (1H, d, J4′-6′=2.4 Hz, H4′), 7.53 (1H, m, H5″), 7.64 (1H, s, H3), 7.84 (1H, s, H2′), 8.29 (1H, d, J6″-5″=4.5 Hz, H6″), 8.49 (1H, m, H4″), 11.73 (1H, s, indolic H); 13C NMR (DMSO, 75.5 MHz): δ (ppm): 55.5 (5′-methoxy), 101.5 (C4′), 109.8 (C2), 110.0 (C3′), 112.5 (C6′), 113.3 (C7′), 117.3 (C1), 118.0 (1C, d, 2JC—F=28 Hz, C3″), 122.3 (1C, d, 4JC—F=4 Hz, C5″), 123.9 (C3a′), 125.8 (C3), 128.1 (C2′), 132.2 (C7a′), 139.4 (1C, d, 3JC—F=3 Hz, C4″), 147.5 (1C, d, 3JC—F=15 Hz, C6″), 154.7 (C5′), 159.7 (1C, d, 1JC—F=270 Hz, C2″); ESI: 294.1 ([M+H]+), 316.1 ([M+Na]+), 348.1 ([M+Na+MeOH]+); HRESI-MS: m/z 316.0861 (calcd for C17H12N3OFNa+, 316.0862).
