[Synthesis]
Under nitrogen protection, 7-aza-indol-2-one (2.00 g, 14.9 mmol) was dissolved in a solvent mixture of DMF (30 mL) and THF (30 mL) and cooled to 0 °C. Sodium hydride (0.600 g, 15.0 mmol) dispersed in 60% mineral oil was slowly added and kept stirring at 0 °C for 1 hour. Subsequently, 2-(trimethylsilyl)ethoxymethyl chloride (3.17 mL, 17.9 mmol) was added dropwise over 3 minutes, the ice bath was withdrawn, and the reaction mixture was allowed to warm up naturally to room temperature and stirring was continued for 21 hours. Upon completion of the reaction, the mixture was poured into water (50 mL) and ethyl acetate (50 mL) for partitioning. The aqueous phase was extracted with ethyl acetate (2 x 50 mL) and the organic phases were combined and washed sequentially with water (2 x 50 mL) and brine (50 mL). The organic layer was dried over anhydrous magnesium sulfate, filtered and concentrated, and purified by Biotage Horizon fast column chromatography (eluent: 25% ethyl acetate/hexane) to afford 1-[[2-(trimethylsilyl)ethoxy]methyl]-1H-pyrrolo[2,3-b]pyridin-2(3H)-one (2.26 g) as a viscous, orange-colored oil.LC-MS analysis Conditions: retention time = 3.49 min; m/z = 265.20 [M+H]+ (column: Phenomenex C18 50×2.0 mm 3 μm; mobile phase A: 90% water:10% methanol:0.1% trifluoroacetic acid; mobile phase B: 10% water:90% methanol:0.1% trifluoroacetic acid; flow rate = 0.8 mL/min; gradient program: (starting B-phase ratio = 0%, final B-phase ratio = 100%, gradient time = 4 min, then held at 100% B-phase for 1 min; column temperature = 40 °C; detection wavelength = 220 nm).1H NMR (400 MHz, DMSO-d6) δ 8.15 (d, J=5.0 Hz, 1H), 7.65 (d, J=7.3 Hz, 1H), 7.05 ( dd, J=7.2,5.4 Hz, 1H), 5.07 (s, 2H), 3.69 (s, 2H), 3.59 (t, J=8.0 Hz, 2H), 0.85 (t, J=8.0 Hz, 2H), -0.06 (s, 9H). |