5-bromo-4,6-difluoro-1H-indole

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution of 5-bromo-4,6-difluoro-1H-indole (285 mg, 1.23 mmol) in DMF (2 mL) was added N-(chloromethylidene)-N-methylmethanaminium (236 mg, 1.84 mmol) at room temperature. The reaction mixture was stirred for 30 min, and treated with additional N-(chloromethylidene)-N-methylmethanaminium (100 mg). The mixture was stirred for an additional 30 minutes at room temperature. The reaction mixture was then treated with 1N aqueous NaOH (2.5 mL) and water (2.5 mL). The mixture was stirred at 100° C. for 30 min. After cooling to room temperature, the solvents were evaporated in vacuo, and the residue was diluted with THF (2 mL) and water (2 mL). The resulting mixture was stirred at room temperature for 2 hours, and the resulting solids were collected by filtration. The solids were washed with water and heptanes and dried in vacuo to give the title compound (157 mg) as a brown solid. MS (ES+) 261.8 ((M+2)+H)+. The mixture was stirred for an additional 30 minutes at room temperature The mixture was stirred at 100° C. for 30 min the solvents were evaporated in vacuo the residue was diluted with THF (2 mL) and water (2 mL) The resulting mixture was stirred at room temperature for 2 hours the resulting solids were collected by filtration The solids were washed with water and heptanes dried in vacuo

反応条件: temp:110.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A solution of 4-bromo-3,5-difluoro-2-[(trimethylsilyl)ethynyl]aniline (1.75 g, 5.77 mmol) in DMF (80 mL) was treated with copper iodide (2.2 g, 11.5 mmol). The reaction mixture was sealed and heated to 110° C. for 3.75 hours. The black reaction mixture was cooled to room temperature, and poured into saturated aqueous ammonium chloride (300 mL). The product was extracted with ethyl acetate/heptane (2:1, 3×200 mL), and the combined organic layers were dried over sodium sulfate, filtered and concentrated in vacuo to give a black oil. The crude product was purified using flash chromatography on silica gel, eluting with heptanes/EtOAc (100:0 to 1:1) to give the title compound (350 mg). MS (ES+) 233.9 ((M+2)+H)+ The reaction mixture was sealed The black reaction mixture was cooled to room temperature The product was extracted with ethyl acetate/heptane (2:1, 3×200 mL) the combined organic layers were dried over sodium sulfate filtered concentrated in vacuo to give a black oil The crude product was purified eluting with heptanes/EtOAc (100:0 to 1:1)

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution of 5-bromo-4,6-difluoro-1H-indole (1.29 g, 5.56 mmol) in acetonitrile (7.0 mL) was added N,N-dimethylformiminium chloride (1.07 g, 8.34 mmol). The reaction mixture was stirred at room temperature for 45 minutes. To the reaction mixture was added 1N NaOH (15 mL, 15 mmol). The resulting mixture was heated to 100° C. for 60 minutes, cooled to 0° C. and the resulting solid was collected via filtration, washed with water, and air-dried with vacuum to provide 900 mg of the title compound. An additional crop of solids formed in the filtrate, was collected, and dried to provide an additional 371 mg of the title compound for a total of 1.271 g (88% yield). MS (ES+) 260.3 (M+H)+. 1H NMR (400 MHz, DMSO-d6) δ 12.58 (br. s, 1H), 9.93 (d, J=3.90 Hz, 2H), 8.34 (s, 2H), 7.39 (dd, J=8.49, 1.07 Hz, 1H). The resulting mixture was heated to 100° C. for 60 minutes cooled to 0° C. the resulting solid was collected via filtration washed with water air-dried with vacuum

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution of 5-bromo-4,6-difluoroindoline (3.6 g, 15.4 mmol) in chloroform (150 mL) was added manganese dioxide (5.3 g, 61 mmol) at room temperature/. The mixture was heated to reflux temperature for 2 hours then cooled to room temperature. The reaction was filtered and the filtrate was concentrated in vacuo. Flash column chromatography was then used to provide the title compound (3.6 g, yield 100%) as brown solid. MS (ES+): 232.0 (M+H). 1H NMR (CDCl3, 400 MHz): δ 8.27 (br. s, 1H), 7.19 (m, 1H), 7.02 (d, 1H), 6.61 (m, 1H). The mixture was heated to reflux temperature for 2 hours The reaction was filtered the filtrate was concentrated in vacuo

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution of 5-bromo-4,6-difluoro-1H-indole (285 mg, 1.23 mmol) in DMF (2 mL) was added N-(chloromethylidene)-N-methylmethanaminium (236 mg, 1.84 mmol) at room temperature. The reaction mixture was stirred for 30 min, and treated with additional N-(chloromethylidene)-N-methylmethanaminium (100 mg). The mixture was stirred for an additional 30 minutes at room temperature. The reaction mixture was then treated with 1 N aqueous NaOH (2.5 mL) and water (2.5 mL). The mixture was stirred at 100° C. for 30 min. After cooling to room temperature, the solvents were evaporated in vacuo, and the residue was diluted with THF (2 mL) and water (2 mL). The resulting mixture was stirred at room temperature for 2 hours, and the resulting solids were collected by filtration. The solids were washed with water and heptanes and dried in vacuo to give the title compound (157 mg) as a brown solid. MS (ES+) 261.8 ((M+2)+H)+. The mixture was stirred for an additional 30 minutes at room temperature The mixture was stirred at 100° C. for 30 min the solvents were evaporated in vacuo the residue was diluted with THF (2 mL) and water (2 mL) The resulting mixture was stirred at room temperature for 2 hours the resulting solids were collected by filtration The solids were washed with water and heptanes dried in vacuo

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution of 5-bromo-4,6-difluoro-1H-indole (285 mg, 1.23 mmol) in DMF (2 mL) was added N-(chloromethylidene)-N-methylmethanaminium (236 mg, 1.84 mmol) at room temperature. The reaction mixture was stirred for 30 min, and treated with additional N-(chloromethylidene)-N-methylmethanaminium (100 mg). The mixture was stirred for an additional 30 minutes at room temperature. The reaction mixture was then treated with 1 N aqueous NaOH (2.5 mL) and water (2.5 mL). The mixture was stirred at 100° C. for 30 min. After cooling to room temperature, the solvents were evaporated in vacuo, and the residue was diluted with THF (2 mL) and water (2 mL). The resulting mixture was stirred at room temperature for 2 hours, and the resulting solids were collected by filtration. The solids were washed with water and heptanes and dried in vacuo to give the title compound (157 mg) as a brown solid. MS (ES+) 261.8 ((M+2)+H)+. The mixture was stirred for an additional 30 minutes at room temperature The mixture was stirred at 100° C. for 30 min the solvents were evaporated in vacuo the residue was diluted with THF (2 mL) and water (2 mL) The resulting mixture was stirred at room temperature for 2 hours the resulting solids were collected by filtration The solids were washed with water and heptanes dried in vacuo

反応条件: temp:110.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A solution of 4-bromo-3,5-difluoro-2-[(trimethylsilyl)ethynyl]aniline (1.75 g, 5.77 mmol) in DMF (80 mL) was treated with copper iodide (2.2 g, 11.5 mmol). The reaction mixture was sealed and heated to 110° C. for 3.75 hours. The black reaction mixture was cooled to room temperature, and poured into saturated aqueous ammonium chloride (300 mL). The product was extracted with ethyl acetate/heptane (2:1, 3×200 mL), and the combined organic layers were dried over sodium sulfate, filtered and concentrated in vacuo to give a black oil. The crude product was purified using flash chromatography on silica gel, eluting with heptanes/EtOAc (100:0 to 1:1) to give the title compound (350 mg). MS (ES+) 233.9 ((M+2)+H)+ The reaction mixture was sealed The black reaction mixture was cooled to room temperature The product was extracted with ethyl acetate/heptane (2:1, 3×200 mL) the combined organic layers were dried over sodium sulfate filtered concentrated in vacuo to give a black oil The crude product was purified eluting with heptanes/EtOAc (100:0 to 1:1)

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution of 5-bromo-4,6-difluoro-1H-indole (1.29 g, 5.56 mmol) in acetonitrile (7.0 mL) was added N,N-dimethylformiminium chloride (1.07 g, 8.34 mmol). The reaction mixture was stirred at room temperature for 45 minutes. To the reaction mixture was added 1N NaOH (15 mL, 15 mmol). The resulting mixture was heated to 100° C. for 60 minutes, cooled to 0° C. and the resulting solid was collected via filtration, washed with water, and air-dried with vacuum to provide 900 mg of the title compound. An additional crop of solids formed in the filtrate, was collected, and dried to provide an additional 371 mg of the title compound for a total of 1.271 g (88% yield). MS (ES+) 260.3 (M+H)+. 1H NMR (400 MHz, DMSO-d6) δ 12.58 (br. s, 1 H), 9.93 (d, J=3.90 Hz, 2 H), 8.34 (s, 2 H), 7.39 (dd, J=8.49, 1.07 Hz, 1 H). The resulting mixture was heated to 100° C. for 60 minutes cooled to 0° C. the resulting solid was collected via filtration washed with water air-dried with vacuum

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution of 5-bromo-4,6-difluoroindoline (3.6 g, 15.4 mmol) in chloroform (150 mL) was added manganese dioxide (5.3 g, 61 mmol) at room temperature/. The mixture was heated to reflux temperature for 2 hours then cooled to room temperature. The reaction was filtered and the filtrate was concentrated in vacuo. Flash column chromatography was then used to provide the title compound (3.6 g, yield 100%) as brown solid. MS (ES+): 232.0 (M+H). 1H NMR (CDCl3, 400 MHz): δ 8.27 (br. s, 1 H), 7.19 (m, 1 H), 7.02 (d, 1 H), 6.61 (m, 1 H). The mixture was heated to reflux temperature for 2 hours The reaction was filtered the filtrate was concentrated in vacuo

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution of 5-bromo-4,6-difluoroindoline (3.6 g, 15.4 mmol) in chloroform (150 mL) was added manganese dioxide (5.3 g, 61 mmol) at room temperature/. The mixture was heated to reflux temperature for 2 hours then cooled to room temperature. The reaction was filtered and the filtrate was concentrated in vacuo. Flash column chromatography was then used to provide the title compound (3.6 g, yield 100%) as brown solid. MS (ES+): 232.0 (M+H). 1H NMR (CDCl3, 400 MHz): δ 8.27 (br. s, 1 H), 7.19 (m, 1 H), 7.02 (d, 1 H), 6.61 (m, 1 H). The mixture was heated to reflux temperature for 2 hours The reaction was filtered the filtrate was concentrated in vacuo

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution of 5-bromo-4,6-difluoro-1H-indole (285 mg, 1.23 mmol) in DMF (2 mL) was added N-(chloromethylidene)-N-methylmethanaminium (236 mg, 1.84 mmol) at room temperature. The reaction mixture was stirred for 30 min, and treated with additional N-(chloromethylidene)-N-methylmethanaminium (100 mg). The mixture was stirred for an additional 30 minutes at room temperature. The reaction mixture was then treated with 1N aqueous NaOH (2.5 mL) and water (2.5 mL). The mixture was stirred at 100° C. for 30 min. After cooling to room temperature, the solvents were evaporated in vacuo, and the residue was diluted with THF (2 mL) and water (2 mL). The resulting mixture was stirred at room temperature for 2 hours, and the resulting solids were collected by filtration. The solids were washed with water and heptanes and dried in vacuo to give the title compound (157 mg) as a brown solid. MS (ES+) 261.8 ((M+2)+H)+. The mixture was stirred for an additional 30 minutes at room temperature The mixture was stirred at 100° C. for 30 min the solvents were evaporated in vacuo the residue was diluted with THF (2 mL) and water (2 mL) The resulting mixture was stirred at room temperature for 2 hours the resulting solids were collected by filtration The solids were washed with water and heptanes dried in vacuo

反応条件: temp:110.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A solution of 4-bromo-3,5-difluoro-2-[(trimethylsilyl)ethynyl]aniline (1.75 g, 5.77 mmol) in DMF (80 mL) was treated with copper iodide (2.2 g, 11.5 mmol). The reaction mixture was sealed and heated to 110° C. for 3.75 hours. The black reaction mixture was cooled to room temperature, and poured into saturated aqueous ammonium chloride (300 mL). The product was extracted with ethyl acetate/heptane (2:1, 3×200 mL), and the combined organic layers were dried over sodium sulfate, filtered and concentrated in vacuo to give a black oil. The crude product was purified using flash chromatography on silica gel, eluting with heptanes/EtOAc (100:0 to 1:1) to give the title compound (350 mg). MS (ES+) 233.9 ((M+2)+H)+ The reaction mixture was sealed The black reaction mixture was cooled to room temperature The product was extracted with ethyl acetate/heptane (2:1, 3×200 mL) the combined organic layers were dried over sodium sulfate filtered concentrated in vacuo to give a black oil The crude product was purified eluting with heptanes/EtOAc (100:0 to 1:1)