2-溴-1-吡咯烷-1-基丙-1-one

反应条件: temp:100.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To a solution of methyl 2-methyl-1H-indole-3-carboxylate (0.52 mmol, 0.1 g) in N,N-dimethylformamide (5 mL), 2-bromo-1-(pyrrolidin-1-yl)propan-1-one (0.52 mmol, 0.137 mg) and cesium carbonate (1.05 mmol, 384 mg) was added. The reaction mixture was heated at 100° C. for 12 hours. LC-MS showed the start material was consumed. The solvent was evaporated and the residue was washed with water (10 ml), extracted with dichloromethane (20 ml). The organic layer was separated, concentrated to give a residue. The residue was purified by column chromatography (silica gel, dichloromethane/methanol=45:1) to give methyl 2-methyl-1-(1-oxo-1-(pyrrolidin-1-yl)propan-2-yl)-1H-indole-3-carboxylate (100 mg, 93%). 1H NMR (300 MHz, CD3OD): δ 8.07-8.03 (m, 1H), 7.44-7.40 (m, 1H), 7.19-7.14 (m, 2H), 5.53-5.49 (m, 1H), 3.90 (s, 3H), 2.80 (s, 3H), 2.00-1.80 (m, 2H), 1.74 (d, J=5.1 Hz, 3H), 1.67-1.64 (m, 4H), 1.32-1.28 (m, 2H). was consumed The solvent was evaporated the residue was washed with water (10 ml) extracted with dichloromethane (20 ml) The organic layer was separated concentrated to give a residue The residue was purified by column chromatography (silica gel, dichloromethane/methanol=45:1)

反应条件: temp:100.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To a solution of methyl 2-methyl-1H-indole-3-carboxylate (0.52 mmol, 0.1 g) in N,N-dimethylformamide (5 mL), 2-bromo-1-(pyrrolidin-1-yl)propan-1-one (0.52 mmol, 0.137 mg) and cesium carbonate (1.05 mmol, 384 mg) was added. The reaction mixture was heated at 100° C. for 12 hours. LC-MS showed the start material was consumed. The solvent was evaporated and the residue was washed with water (10 ml), extracted with dichloromethane (20 ml). The organic layer was separated, concentrated to give a residue. The residue was purified by column chromatography (silica gel, dichloromethane/methanol=45:1) to give methyl 2-methyl-1-(1-oxo-1-(pyrrolidin-1-yl)propan-2-yl)-1H-indole-3-carboxylate (100 mg, 93%). 1H NMR (300 MHz, CD3OD): δ 8.07-8.03 (m, 1H), 7.44-7.40 (m, 1H), 7.19-7.14 (m, 2H), 5.53-5.49 (m, 1H), 3.90 (s, 3H), 2.80 (s, 3H), 2.00-1.80 (m, 2H), 1.74 (d, J=5.1 Hz, 3H), 1.67-1.64 (m, 4H), 1.32-1.28 (m, 2H). was consumed The solvent was evaporated the residue was washed with water (10 ml) extracted with dichloromethane (20 ml) The organic layer was separated concentrated to give a residue The residue was purified by column chromatography (silica gel, dichloromethane/methanol=45:1)

反应条件: temp:100.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To a solution of methyl 2-methyl-1H-indole-3-carboxylate (0.52 mmol, 0.1 g) in N,N-dimethylformamide (5 mL), 2-bromo-1-(pyrrolidin-1-yl)propan-1-one (0.52 mmol, 0.137 mg) and cesium carbonate (1.05 mmol, 384 mg) was added. The reaction mixture was heated at 100° C. for 12 hours. LC-MS showed the start material was consumed. The solvent was evaporated and the residue was washed with water (10 ml), extracted with dichloromethane (20 ml). The organic layer was separated, concentrated to give a residue. The residue was purified by column chromatography (silica gel, dichloromethane/methanol=45:1) to give methyl 2-methyl-1-(1-oxo-1-(pyrrolidin-1-yl)propan-2-yl)-1H-indole-3-carboxylate (100 mg, 93%). 1H NMR (300 MHz, CD3OD): δ 8.07-8.03 (m, 1H), 7.44-7.40 (m, 1H), 7.19-7.14 (m, 2H), 5.53-5.49 (m, 1H), 3.90 (s, 3H), 2.80 (s, 3H), 2.00-1.80 (m, 2H), 1.74 (d, J=5.1 Hz, 3H), 1.67-1.64 (m, 4H), 1.32-1.28 (m, 2H). was consumed The solvent was evaporated the residue was washed with water (10 ml) extracted with dichloromethane (20 ml) The organic layer was separated concentrated to give a residue The residue was purified by column chromatography (silica gel, dichloromethane/methanol=45:1)

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

实验步骤: Pyrrolidine (0.12 mol, 8.3 g) was added to stirred solution of 2-bromopropanoyl chloride (0.58 mol, 10 g) in dichloromethane (200 ml) at 0° C. After 0.5 hour, the reaction mixture was warmed to room temperature, stirred for 2 hours, and saturated ammonium chloride solution (20 ml) was added. The solvent was evaporated and the mixture was extracted with ethyl acetate (200 ml). The organic phase was separated, dried over anhydrous sodium sulfate, filtered and concentrated to dryness. The residue was purified by column chromatography (silica gel, dichloromethane/methanol=55:1) to give 2-bromo-1-(pyrrolidin-1-yl)propan-1-one (9.8 g, 93%). LCMS (M+H+) m/z: calcd 205.01. found 205. The solvent was evaporated the mixture was extracted with ethyl acetate (200 ml) The organic phase was separated dried over anhydrous sodium sulfate filtered concentrated to dryness The residue was purified by column chromatography (silica gel, dichloromethane/methanol=55:1)

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

实验步骤: Pyrrolidine (0.12 mol, 8.3 g) was added to stirred solution of 2-bromopropanoyl chloride (0.58 mol, 10 g) in dichloromethane (200 ml) at 0° C. After 0.5 hour, the reaction mixture was warmed to room temperature, stirred for 2 hours, and saturated ammonium chloride solution (20 ml) was added. The solvent was evaporated and the mixture was extracted with ethyl acetate (200 ml). The organic phase was separated, dried over anhydrous sodium sulfate, filtered and concentrated to dryness. The residue was purified by column chromatography (silica gel, dichloromethane/methanol=55:1) to give 2-bromo-1-(pyrrolidin-1-yl)propan-1-one (9.8 g, 93%). LCMS (M+H+) m/z: calcd 205.01. found 205. The solvent was evaporated the mixture was extracted with ethyl acetate (200 ml) The organic phase was separated dried over anhydrous sodium sulfate filtered concentrated to dryness The residue was purified by column chromatography (silica gel, dichloromethane/methanol=55:1)

反应条件: temp:45.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To a solution of 6.35 g (40.1 mmol) potassium 2-vinylphenolate in 110 mL of water (pH adjusted to 14 by addition of KOH) under argon was added 150 mL of toluene, 0.65 g (2.0 mmol) of tetrabutylammonium bromide and 11.54 g (50.16 mmol) of 2-bromo-1-pyrrolidin-1-yl-propan-1-one. The two-phase mixture was stirred vigorously over night at 45° C. After this time the organic phase was removed, washed with water, 4 M sodium hydroxide aqueous solution, 1 M hydrochloric acid solution and water, dried (Na2SO4), and evaporated to dryness. Crystallization of the residue from warm heptane (200 mL) afforded the title compound as a white powder (7.0 g, 70.5% yield): MP 85-86° C., MS: 246.1496 (M+H)+, 268.1317 (M+Na)+. After this time the organic phase was removed washed with water, 4 M sodium hydroxide aqueous solution, 1 M hydrochloric acid solution and water dried (Na2SO4) evaporated to dryness Crystallization of the residue from warm heptane (200 mL)

反应条件: temp:100.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To a solution of methyl 2-methyl-1H-indole-3-carboxylate (0.52 mmol, 0.1 g) in N,N-dimethylformamide (5 mL), 2-bromo-1-(pyrrolidin-1-yl)propan-1-one (0.52 mmol, 0.137 mg) and cesium carbonate (1.05 mmol, 384 mg) was added. The reaction mixture was heated at 100° C. for 12 hours. LC-MS showed the start material was consumed. The solvent was evaporated and the residue was washed with water (10 ml), extracted with dichloromethane (20 ml). The organic layer was separated, concentrated to give a residue. The residue was purified by column chromatography (silica gel, dichloromethane/methanol=45:1) to give methyl 2-methyl-1-(1-oxo-1-(pyrrolidin-1-yl)propan-2-yl)-1H-indole-3-carboxylate (100 mg, 93%). 1H NMR (300 MHz, CD3OD): δ 8.07-8.03 (m, 1H), 7.44-7.40 (m, 1H), 7.19-7.14 (m, 2H), 5.53-5.49 (m, 1H), 3.90 (s, 3H), 2.80 (s, 3H), 2.00-1.80 (m, 2H), 1.74 (d, J=5.1 Hz, 3H), 1.67-1.64 (m, 4H), 1.32-1.28 (m, 2H). was consumed The solvent was evaporated the residue was washed with water (10 ml) extracted with dichloromethane (20 ml) The organic layer was separated concentrated to give a residue The residue was purified by column chromatography (silica gel, dichloromethane/methanol=45:1)

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

实验步骤: Pyrrolidine (0.12 mol, 8.3 g) was added to stirred solution of 2-bromopropanoyl chloride (0.58 mol, 10 g) in dichloromethane (200 ml) at 0° C. After 0.5 hour, the reaction mixture was warmed to room temperature, stirred for 2 hours, and saturated ammonium chloride solution (20 ml) was added. The solvent was evaporated and the mixture was extracted with ethyl acetate (200 ml). The organic phase was separated, dried over anhydrous sodium sulfate, filtered and concentrated to dryness. The residue was purified by column chromatography (silica gel, dichloromethane/methanol=55:1) to give 2-bromo-1-(pyrrolidin-1-yl)propan-1-one (9.8 g, 93%). LCMS (M+H+) m/z: calcd 205.01. found 205. The solvent was evaporated the mixture was extracted with ethyl acetate (200 ml) The organic phase was separated dried over anhydrous sodium sulfate filtered concentrated to dryness The residue was purified by column chromatography (silica gel, dichloromethane/methanol=55:1)