3-bromo-4-fluorobenzenesulfonyl chloride

反応条件: temp:0.00; pressure:0.00; stir:

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

実験手順: A solution of 3-bromo-4-fluorobenzene-1-sulfonyl chloride (Combi-blocks) (250 mg, 0.91 mmol), N,N-dimethylpyrrolidin-3-amine (218 mg, 1.9 mmol) in tetrahydrofuran (5.7 mL) was stirred at ambient temperature for 16 hours. The solvent was evaporated and residue was purified by flash chromatography (silica gel, dichloromethane/gradient with MeOH) to afford the title compound (220 mg, 69% yield). The solvent was evaporated residue was purified by flash chromatography (silica gel, dichloromethane/gradient with MeOH)

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

実験手順: A solution of 3-bromo-4-fluorobenzene-1-sulfonyl chloride (Combi-blocks) (250 mg, 0.91 mmol), N,N-dimethylpyrrolidin-3-amine (218 mg, 1.9 mmol) in tetrahydrofuran (5.7 mL) was stirred at ambient temperature for 16 hours. The solvent was evaporated and residue was purified by flash chromatography (silica gel, dichloromethane/gradient with MeOH) to afford the title compound (220 mg, 69% yield). The solvent was evaporated residue was purified by flash chromatography (silica gel, dichloromethane/gradient with MeOH)

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

実験手順: To a suspension of 3,3-difluoroazetidine hydrochloric acid (0.947 g, 7.31 mmol) in 20 mL dichloromethane at 0° C. was added N-ethyl-N-isopropylpropan-2-amine (2.80 mL, 16.1 mmol) followed by the addition of a solution of 3-bromo-4-fluorobenzene-1-sulfonyl chloride (2.0 g, 7.3 mmol) in 4 mL dichloromethane. The mixture was stirred at room temperature overnight and then heated at 55° C. for 5 hours, diluted with dichloromethane, washed with water, dried over anhydrous magnesium sulfate, and filtered. The filtrate was concentrated and the residue was purified by flash chromatography (silica gel, 10-50% ethyl acetate/heptanes gradient) to give the title compound (1.5 g, 62.1% yield) heated at 55° C. for 5 hours washed with water dried over anhydrous magnesium sulfate filtered The filtrate was concentrated the residue was purified by flash chromatography (silica gel, 10-50% ethyl acetate/heptanes gradient)

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

実験手順: A solution of 3-bromo-4-fluorobenzene-1-sulfonyl chloride (Aldrich) (2.53 g, 8.33 mmol), indoline (0.99 g, 8.33 mmol), N,N-diisopropylethylamine (1.60 mL, 9.16 mmol) and tetrahydrofuran (20 mL) was stirred at ambient temperature for 16 hours. The reaction mixture was partitioned between water and ethyl acetate. The aqueous layer was extracted twice with additional ethyl acetate. The combined organic layers were washed with saturated aqueous sodium chloride, dried over anhydrous magnesium sulfate, filtered, and concentrated to afford a brown oil which solidified upon standing. The crude product was recrystallized from ether/heptane to afford the title compound (1.99 g, 5.59 mmol, 67% yield). The reaction mixture was partitioned between water and ethyl acetate The aqueous layer was extracted twice with additional ethyl acetate The combined organic layers were washed with saturated aqueous sodium chloride dried over anhydrous magnesium sulfate filtered concentrated to afford a brown oil which The crude product was recrystallized from ether/heptane

反応条件: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution of 3-bromo-4-fluorobenzene-1-sulfonyl chloride (1.0 g, 3.66 mmol) in 20 mL dichloromethane at 0° C. was added pyrrolidine (0.635 mL, 7.68 mmol). The mixture was stirred at 0° C. for 30 minutes and then at room temperature overnight. The reaction mixture was diluted with dichloromethane, washed with 1% HCl solution and water, dried over anhydrous magnesium sulfate, filtered, and concentrated to give the title compound (0.86 g, 76% yield) at room temperature overnight washed with 1% HCl solution and water dried over anhydrous magnesium sulfate filtered concentrated

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

実験手順: 3-Bromo-4-fluorobenzene-1-sulfonyl chloride (0.44 g, 1.609 mmol) in tetrahydrofuran (10 mL) was treated with morpholine (0.294 g, 3.38 mmol). The reaction mixture was stirred for 16 hours at ambient temperature. The solvent was removed, and the residue was loaded onto a silica gel column and eluted with 20% ethyl acetate in hexanes to give the title compound (0.45 g, 1.388 mmol, 86% yield). The solvent was removed eluted with 20% ethyl acetate in hexanes

反応条件: temp:-78.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 3-Bromo-4-fluoro-benzenesulfonyl chloride ((Example 319: part b) 1.9 g, 6.83 mmol) and sodium bicarbonate (1.15 g, 13.66 mmol) was suspended in 16 mL of water at 70° C. A solution of sodium sulfite (1.64 g, 13 mmol) in 15 mL of water was added in 3 portions over 3 h. The mixture was stirred for 16 h, and the solvent was removed in vacuo. DMF (15 mL) was added, the mixture was stirred for 15 min, and the inorganic salts were then allowed to settle. The DMF was removed via syringe, the salts were washed with a second portion of DMF (10 mL), and the combined DMF solution was slowly added to a 0° C. solution of 4-bromo-5-nitro-thiophene-2-carboxylic acid methyl ester ((Example 114, step c) 931 mg, 3.5 mmol) in DMF (15 mL). The solution was stirred for 0° C. for 1 h. The DMF was removed in vacuo and the residue was partitioned between EtOAc (100 mL) and aq NaHCO3 (30 mL). The layers were separated and the organic layer was washed with aq NaHCO3 (2×20 mL), water (30 mL), and brine (30 mL), then dried over sodium sulfate. The solution was concentrated and the residue (1.42 g) was dissolved in THF (20 mL) and cooled to −78° C. A solution of sodium methoxide in methanol (1M, 5 mL, 5 mmol) was added dropwise and the reaction was stirred for 30 min at −78° C. Acetic acid (500 μL) was added followed by EtOAc (100 mL). The solution was washed with NaHCO3 (3×30 mL), brine (40 mL), and was dried over sodium sulfate. Concentration and chromatography of the residue yielded the title compound (502 mg, 17%) as a yellow solid. 1H-NMR (CDCl3): δ 8.16 (dd, 1H, J=2.3, 6.3 Hz), 7.94 (s, 1H), 7.91 (ddd, 1H, J=2.6, 4.4, 8.6 Hz), 7.39 (dd, 1H, J=5.3, 8.6 Hz). the solvent was removed in vacuo DMF (15 mL) was added the mixture was stirred for 15 min The DMF was removed via syringe the salts were washed with a second portion of DMF (10 mL) The solution was stirred for 0° C. for 1 h The DMF was removed in vacuo the residue was partitioned between EtOAc (100 mL) and aq NaHCO3 (30 mL) The layers were separated the organic layer was washed with aq NaHCO3 (2×20 mL), water (30 mL), and brine (30 mL) dried over sodium sulfate The solution was concentrated the residue (1.42 g) was dissolved in THF (20 mL) the reaction was stirred for 30 min at −78° C The solution was washed with NaHCO3 (3×30 mL), brine (40 mL) was dried over sodium sulfate Concentration and chromatography of the residue

反応条件: temp:-5.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Concentrated HCl (1.93 mL, 23.16 mmol) was added to a solution of 3-bromo-4-fluoro-phenylamine ((Example 265: part a) 2.2 g, 11.58 mmol) in 18 mL of 2:1 DCM/MeOH. A precipitate appeared and another 9 mL of 2:1 DCM/MeOH was added. The solution was cooled to −5° C. and tert-butylnitrate (2.71 mL, 23.16 mmol) was added dropwise over 8 min. After stirring for 15 min, sulfur dioxide (˜5 mL) was condensed into the reaction, followed by addition of copper(II) chloride (592 mg, 3.47 mmol) (gas evolution). The solvent was removed in vacuo and the residue was purified by SiO2 flash column chromatography to yield the title compound (1.9 g, 59%). 1H-NMR (CDCl3): δ 8.31 (dd, 1H, J=2.3, 5.8 Hz), 8.04 (ddd, 1H, J=2.6, 4.1, 8.8 Hz), 7.39 (dd, 1H, J=7.7, 8.8 Hz). condensed into the reaction The solvent was removed in vacuo the residue was purified by SiO2 flash column chromatography

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

実験手順: To a solution of 3-bromo-4-fluorobenzene-1-sulfonyl chloride (0.83 g, 2.73 mmol) in tetrahydrofuran (10 mL) under argon was added diisopropylethylamine (0.525 mL, 3.00 mmol) followed by pyrrolidine (0.183 mL, 2.73 mmol). The reaction mixture was stirred at ambient temperature for 2 hours. The reaction mixture was partitioned between diethyl ether and aqueous ammonium chloride. The organic layer was separated, dried over anhydrous magnesium sulfate, filtered, and concentrated. The resulting residue was triturated with diethyl ether/heptane at −20° C. to provide the title compound (0.56 g, 67% yield). The reaction mixture was partitioned between diethyl ether and aqueous ammonium chloride The organic layer was separated dried over anhydrous magnesium sulfate filtered concentrated The resulting residue was triturated with diethyl ether/heptane at −20° C.

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

実験手順: To a solution of 3-bromo-4-fluorobenzene-1-sulfonyl chloride (0.83 g, 2.73 mmol) in tetrahydrofuran (10 mL) under argon was added diisopropylethylamine (0.525 mL, 3.00 mmol) followed by pyrrolidine (0.183 mL, 2.73 mmol). The reaction mixture was stirred at ambient temperature for 2 hours. The reaction mixture was partitioned between diethyl ether and aqueous ammonium chloride. The organic layer was separated, dried over anhydrous magnesium sulfate, filtered, and concentrated. The resulting residue was triturated with diethyl ether/heptane at −20° C. to provide the title compound (0.56 g, 67% yield). The reaction mixture was partitioned between diethyl ether and aqueous ammonium chloride The organic layer was separated dried over anhydrous magnesium sulfate filtered concentrated The resulting residue was triturated with diethyl ether/heptane at −20° C.

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

実験手順: A mixture of 3-bromo-4-fluorobenzene-1-sulfonyl chloride (2.53 g, 8.33 mmol), indoline (0.933 mL, 8.33 mmol), and N,N-diisopropylethyl-amine (1.60 mL, 9.16 mmol) in tetrahydrofuran (20 mL) was stirred at room temperature for 20 hours. The reaction mixture was partitioned between water and ether. The organic layer was washed with saturated aqueous sodium chloride, dried over anhydrous magnesium sulfate, filtered, and concentrated to a solid residue. Recrystallization from ether and heptane provided the title compound (1.99 g, 67%). The reaction mixture was partitioned between water and ether The organic layer was washed with saturated aqueous sodium chloride dried over anhydrous magnesium sulfate filtered concentrated to a solid residue Recrystallization from ether and heptane