1,2-Dimethoxyethane → HCID 66793981, compound

Participants

Reaction Conditions

Reaction Steps

To 4-methoxy-1-methyl-5-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-1,3-dihydro-indol-2-one, prepared as described in Example 37a (80 mg, 0.264 mmol) was added (5-bromo-pyridin-3-yl)-methanol (CAS#37669-64-0, 55 mg, 0.29 mmol), 1,2-dimethoxyethane (3.0 mL), and 2 M aqueous sodium carbonate (0.330 mL, 066 mmol). The reaction mixture was degassed and placed under an argon atmosphere, at which time resin bound tetrakis(triphenylphosphine)palladium(0), specifically polystyrene triphenylphosphine palladium (0) [PS—PPh3-Pd(0) (Biotage), 0.11 mmol/g loading, (120 mg, 0.013 mmol)] was added. The reaction vessel was sealed and was heated by microwave irradiation at 120° C. for 3 hours. The reaction mixture was then cooled to room temperature, diluted with dichloromethane and filtered through glass wool. The filtrate was further diluted with saturated aqueous sodium bicarbonate and the layers were separated. The aqueous layer was extracted two times with dichloromethane, and the organic layers were combined, dried over anhydrous sodium sulfate, filtered and concentrated. The resulting residue was partially purified by silica gel flash chromatography (ethanol-dichloromethane, 0 to 10%). Further purification was accomplished via reverse phase HPLC (7 to 40% acetonitrile/water w/0.1% NH4OH) to furnish 5-(5-hydroxymethyl-pyridin-3-yl)-4-methoxy-1-methyl-1,3-dihydro-indol-2-one; HRMS: (ESI) m/z 285.1240 (M+H)+; 1H NMR (400 MHz, CD3OD) δ ppm 3.24 (s, 3H), 3.75 (s, 3H), 3.78 (s, 2H), 4.71 (s, 2H), 6.84 (d, J=81 Hz, 1H), 7.34 (d, J=8.1 Hz, 1H), 7.94 (d, J=2.0 Hz, 1H), 8.45 (d, J=1.8 Hz, 1H), 8.55 (d, J=2.0 Hz, 1H)

Provenance & Evidence