3,4,5-trifluorobenzenesulfonyl chloride

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:-10.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: The flask containing the SOCl2/H2O solution is cooled again to −10° C. and a catalytic amount of Cu(I)Cl (˜50 mg) was added. The solution turns dark green in color. The flask was fitted with a 500 mL addition funnel (previously chilled to 0° C.) and the 3,4,5-trifluorodiazobenzene solution was quickly transferred to the funnel. The solution was immediately added dropwise over a period of 3 min. After addition, the reaction mixture slowly turns darker green in color, but after stirring for 5 min becomes bright, lime green. The reaction was stirred for an additional hour while warming to room temperature. The reaction mixture was transferred to a separatory funnel and extracted with CH2Cl2 (3×200 mL). The organic phases are combined and dried over anhydrous Na2SO4, filtered, and concentrated to give a dark-bronze oil (79.5 g, 83%). The flask was fitted with a 500 mL addition funnel ( The solution was immediately added dropwise over a period of 3 min After addition The reaction was stirred for an additional hour while warming to room temperature The reaction mixture was transferred to a separatory funnel extracted with CH2Cl2 (3×200 mL) dried over anhydrous Na2SO4 filtered concentrated

反応条件: temp:-10.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: The flask containing the SOCl2/H2O solution is cooled again to −10° C. and a catalytic amount of Cu(I)Cl (˜50 mg) was added. The solution turns dark green in color. The flask was fitted with a 500 mL addition funnel (previously chilled to 0° C.) and the 3,4,5-trifluorodiazobenzene solution was quickly transferred to the funnel. The solution was immediately added dropwise over a period of 3 min. After addition, the reaction mixture slowly turns darker green in color, but after stirring for 5 min becomes bright, lime green. The reaction was stirred for an additional hour while warming to room temperature. The reaction mixture was transferred to a separatory funnel and extracted with CH2Cl2 (3×200 mL). The organic phases are combined and dried over anhydrous Na2SO4, filtered, and concentrated to give a dark-bronze oil (79.5 g, 83%). The flask was fitted with a 500 mL addition funnel ( The solution was immediately added dropwise over a period of 3 min After addition The reaction was stirred for an additional hour while warming to room temperature The reaction mixture was transferred to a separatory funnel extracted with CH2Cl2 (3×200 mL) dried over anhydrous Na2SO4 filtered concentrated

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: To a solution of N-(2,4-dimethoxybenzyl)-1,2,4-thiadiazol-5-amine (2.8 g, 13 mmol) in tetrahydrofuran (50 mL) at −78° C. was added lithium bis(trimethylsilyl)amide (1 M solution in tetrahydrofuran, 15.6 mL, 15.6 mmol). The reaction mixture was allowed to warm to ambient temperature and stirred for 1 h. The reaction mixture was then cooled to −78° C. and 3,4,5-trifluorobenzene-1-sulfonyl chloride (3.0 g, 13.0 mmol) was added. The mixture was stirred at −78° C. for 0.5 h, warmed to 0° C. and 4,5-trifluorobenzene-1-sulfonyl chloride (0.6 g, 2.6 mmol) was added. The mixture was allowed to warm to ambient temperature, stirred for 20 h, diluted with ethyl acetate (200 mL), washed with saturated aqueous ammonium chloride (200 mL) and brine (200 mL), dried over sodium sulphate, filtered and concentrated in vacuo. The residue was triturated with dichloromethane to afford N-(2,4-dimethoxybenzyl)-3,4,5-trifluoro-N-(1,2,4-thiadiazol-5-yl)benzenesulfonamide as a beige solid in 53% yield (3.1 g): 1H NMR (300 MHz, CDCl3) δ8.24-8.18 (m, 1H), 7.37-7.28 (m, 2H), 7.26-7.22 (m, 1H), 7.07 (d, J=8.1 Hz, 1H), 6.39-6.32 (m, 1H), 6.29-6.24 (m, 1H), 5.27 (s, 2H), 3.75 (s, 3H), 3.65 (s, 3H). The reaction mixture was then cooled to −78° C. The mixture was stirred at −78° C. for 0.5 h warmed to 0° C. to warm to ambient temperature stirred for 20 h washed with saturated aqueous ammonium chloride (200 mL) and brine (200 mL) dried over sodium sulphate filtered concentrated in vacuo The residue was triturated with dichloromethane

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

実験手順: To a solution of N-(2,4-dimethoxybenzyl)-1,2,4-thiadiazol-5-amine (2.8 g, 13 mmol) in tetrahydrofuran (50 mL) at −78° C. was added lithium bis(trimethylsilyl)amide (1 M solution in tetrahydrofuran, 15.6 mL, 15.6 mmol). The reaction mixture was allowed to warm to ambient temperature and stirred for 1 h. The reaction mixture was then cooled to −78° C. and 3,4,5-trifluorobenzene-1-sulfonyl chloride (3.0 g, 13.0 mmol) was added. The mixture was stirred at −78° C. for 0.5 h, warmed to 0° C. and 4,5-trifluorobenzene-1-sulfonyl chloride (0.6 g, 2.6 mmol) was added. The mixture was allowed to warm to ambient temperature, stirred for 20 h, diluted with ethyl acetate (200 mL), washed with saturated aqueous ammonium chloride (200 mL) and brine (200 mL), dried over sodium sulphate, filtered and concentrated in vacuo. The residue was triturated with dichloromethane to afford N-(2,4-dimethoxybenzyl)-3,4,5-trifluoro-N-(1,2,4-thiadiazol-5-yl)benzenesulfonamide as a beige solid in 53% yield (3.1 g): 1H NMR (300 MHz, CDCl3) δ8.24-8.18 (m, 1H), 7.37-7.28 (m, 2H), 7.26-7.22 (m, 1H), 7.07 (d, J=8.1 Hz, 1H), 6.39-6.32 (m, 1H), 6.29-6.24 (m, 1H), 5.27 (s, 2H), 3.75 (s, 3H), 3.65 (s, 3H). The reaction mixture was then cooled to −78° C. The mixture was stirred at −78° C. for 0.5 h warmed to 0° C. to warm to ambient temperature stirred for 20 h washed with saturated aqueous ammonium chloride (200 mL) and brine (200 mL) dried over sodium sulphate filtered concentrated in vacuo The residue was triturated with dichloromethane

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

実験手順: The title compound, MS: m/e=500.0 (M+H+), was prepared in accordance with the general method of example 13 from 5-nitro-2-chloroquinoline, 3,4,5-trifluorobenzenesulfonyl chloride and rac-7-methoxy-indane-1-ylamine.

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

実験手順: The title compound, MS: m/e=500.4 (M+H+), was prepared in accordance with the general method of example 13 from 5-nitro-2-chloroquinoline, 3,4,5-trifluorobenzenesulfonyl chloride and 6-methoxyindan-1-ylamine (CAS 103028-81-5).

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

実験手順: The title compound, MS: m/e=470.5 (M+H+), was prepared in accordance with the general method of example 13 from 5-nitro-2-chloroquinoline, 3,4,5-trifluorobenzenesulfonyl chloride and 2-aminoindane.

反応条件: temp:25.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A solution of 3,4,5-trifluorobenzenesulfonyl chloride (0.348 mL, 2.50 mmol) in CH2Cl2 (5 mL) was added to a solution of 2-amino-4,4,4-trifluoro-3-trifluoromethyl-butyric acid ethyl ester (0.4 g, 1.67 mmol) prepared as described (J. Med Chem. 1981, 24, 1043-1047), and pyridine (0.27 mL, 3.34 mmol) in CH2Cl2 (5 mL) at 0° C. and allowed to warm to 25° C. for 19 h. The solution was washed with 1M HCl (1 mL), brine (1 mL), dried over Na2SO4 and concentrated. The crude solid was purified by Biotage Flash™ chromatography, eluting with EtOAc/hexanes (1:4), to give 4,4,4-trifluoro-2-(3,4,5-trifluoro-benzenesulfonylamino)-3-trifluoromethyl-butyric acid ethyl ester (0.63 g, 85%) as a white solid. Mass Spectrum (+ESI): 448 [M+H]+. prepared at 0° C. The solution was washed with 1M HCl (1 mL), brine (1 mL) dried over Na2SO4 concentrated The crude solid was purified by Biotage Flash™ chromatography eluting with EtOAc/hexanes (1:4)

反応条件: temp:-10.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: The flask containing the SOCl2/H2O solution is cooled again to −10° C. and a catalytic amount of Cu(I)Cl (˜50 mg) was added. The solution turns dark green in color. The flask was fitted with a 500 mL addition funnel (previously chilled to 0° C.) and the 3,4,5-trifluorodiazobenzene solution was quickly transferred to the funnel. The solution was immediately added dropwise over a period of 3 min. After addition, the reaction mixture slowly turns darker green in color, but after stirring for 5 min becomes bright, lime green. The reaction was stirred for an additional hour while warming to room temperature. The reaction mixture was transferred to a separatory funnel and extracted with CH2Cl2 (3×200 mL). The organic phases are combined and dried over anhydrous Na2SO4, filtered, and concentrated to give a dark-bronze oil (79.5 g, 83%). The flask was fitted with a 500 mL addition funnel ( The solution was immediately added dropwise over a period of 3 min After addition The reaction was stirred for an additional hour while warming to room temperature The reaction mixture was transferred to a separatory funnel extracted with CH2Cl2 (3×200 mL) dried over anhydrous Na2SO4 filtered concentrated

反応条件: temp:-10.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: The flask containing the SOCl2/H2O solution is cooled again to −10° C. and a catalytic amount of Cu(I)Cl (˜50 mg) was added. The solution turns dark green in color. The flask was fitted with a 500 mL addition funnel (previously chilled to 0° C.) and the 3,4,5-trifluorodiazobenzene solution was quickly transferred to the funnel. The solution was immediately added dropwise over a period of 3 min. After addition, the reaction mixture slowly turns darker green in color, but after stirring for 5 min becomes bright, lime green. The reaction was stirred for an additional hour while warming to room temperature. The reaction mixture was transferred to a separatory funnel and extracted with CH2Cl2 (3×200 mL). The organic phases are combined and dried over anhydrous Na2SO4, filtered, and concentrated to give a dark-bronze oil (79.5 g, 83%). The flask was fitted with a 500 mL addition funnel ( The solution was immediately added dropwise over a period of 3 min After addition The reaction was stirred for an additional hour while warming to room temperature The reaction mixture was transferred to a separatory funnel extracted with CH2Cl2 (3×200 mL) dried over anhydrous Na2SO4 filtered concentrated