5-bromo-4-methoxy-1-methyl-3H-indol-2-one

Conditions: temp:120.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To 5-bromo-4-methoxy-1-methyl-1,3-dihydro-indol-2-one (105 mg, 0.410 mmol) was added 3-pyridineboronic acid (CAS#1692-25-7, 60.5 mg, 0.492 mmol), 1,2-dimethoxyethane (3 mL) and 2 M aqueous sodium carbonate (0.513 ml, 1.025 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, (186 mg, 0.021 mmol)] was added. The reaction vessel was sealed and was heated by microwave irradiation at 120° C. for 2.25 hours. The reaction mixture was 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 purified by silica gel flash chromatography (ethyl acetate-dichloromethane, 20 to 100%) to afford 4-methoxy-1-methyl-5-pyridin-3-yl-1,3-dihydro-indol-2-one; HRMS: (ESI) m/z 255.1136 (M+H)4; 1H NMR (400 MHz, CO2Cl2) δ ppm 3.20 (s, 3H), 3.66 (s, 2H), 3.72 (s, 3H), 6.68 (d, J=8.0 Hz, 1H), 7.28 (d, J=8.0 Hz, 1H), 7.38 (dd, J=7.9, 4.9 Hz, 1H), 7.79-7.96 (m, 1H), 8.52 (d, J=4.0 Hz, 1H), 8.71 (s, 1H). The reaction mixture was degassed was added The reaction vessel was sealed The reaction mixture was cooled to room temperature filtered through glass wool The filtrate was further diluted with saturated aqueous sodium bicarbonate the layers were separated The aqueous layer was extracted two times with dichloromethane dried over anhydrous sodium sulfate filtered concentrated The resulting residue was purified by silica gel flash chromatography (ethyl acetate-dichloromethane, 20 to 100%)

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 4-methoxy-1-methyl-1,3-dihydro-indol-2-one (440 mg, 2.483 mmol) in chloroform (25 ml) was added methanol (25.00 ml). The reaction was put at −10° C. and N-bromosuccinimide (442 mg, 2.483 mmol) was added in three portions over a 30 min interval and the reaction was then stirred for 10 minutes. The reaction was then diluted with dichloromethane, saturated aqueous sodium bicarbonate, and saturated aqueous sodium thiosulfate and the layers were separated. The aqueous layer was extracted two additional times with dichloromethane and the organic layers were combined, dried over anhydrous sodium sulfate, filtered, and concentrated. The resulting residue was purified by silica gel flash chromatography (ethyl acetate-heptane, 0 to 60%) to afford 5-bromo-4-methoxy-1-methyl-1,3-dihydro-indol-2-one; MS: (ES+) m/z 255.8 (M+H)+. was put at −10° C. the layers were separated The aqueous layer was extracted two additional times with dichloromethane dried over anhydrous sodium sulfate filtered concentrated The resulting residue was purified by silica gel flash chromatography (ethyl acetate-heptane, 0 to 60%)