N-propylsulfamoyl chloride

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:

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 mixture of the product from Step 6 (100 mg, 0.27 mmol), triethylamine (110 mg, 1.1 mmol) and propylsulfamoyl chloride (170 mg, 1.1 mmol) in DCM (5 ml) was stirred at ambient temperature for 18 hrs. The reaction mixture was diluted with water (20 ml) and extracted with ethyl acetate (3×20 ml). The organic extracts were washed with brine (50 ml), dried over MgSO4 and concentrated in vacuo. The residue was purified by flash chromatography eluting with ethyl acetate: hexane (1:4) to afford N-(3-chloro-4-{(E)-2-[5-(4-fluorophenyl)-1-methyl-1H-pyrazol-3-yl]vinyl}bicyclo[4.2.1]non-3-en-9-yl)-N-propylsulfamide (98 mg, 74%). δH (400 MHz, CDCl3) 0.98 (3H, t, J 7.5), 1.42-1.48 (1H, m), 1.54-1.62 (4H, m), 1.82-1.90 (2H, m), 2.38-2.62 (3H, m), 2.68-2.76 (2H, m), 2.98-3.08 (3H, m), 3.72-3.77 (1H, m), 3.82 (2H, s), 4.13-4.18 (1H, m), 4.33 (1H, d, J 9.0), 6.48 (1H, s), 6.64 (1H, d, J 16.5), 7.12-7.18 (2H, m), 7.37-7.43 (2H, m), 7.45 (1H, d, J 16.5). extracted with ethyl acetate (3×20 ml) The organic extracts were washed with brine (50 ml) dried over MgSO4 concentrated in vacuo The residue was purified by flash chromatography eluting with ethyl acetate: hexane (1:4)

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

実験手順: A mixture of the product from Step 6 (100 mg, 0.27 mmol), triethylamine (110 mg, 1.1 mmol) and propylsulfamoyl chloride (170 mg, 1.1 mmol) in DCM (5 ml) was stirred at ambient temperature for 18 hrs. The reaction mixture was diluted with water (20 ml) and extracted with ethyl acetate (3×20 ml). The organic extracts were washed with brine (50 ml), dried over MgSO4 and concentrated in vacuo. The residue was purified by flash chromatography eluting with ethyl acetate: hexane (1:4) to afford N-(3-chloro-4-{(E)-2-[5-(4-fluorophenyl)-1-methyl-1H-pyrazol-3-yl]vinyl}bicyclo[4.2.1]non-3-en-9-yl)-N-propylsulfamide (98 mg, 74%). δH (400 MHz, CDCl3) 0.98 (3H, t, J 7.5), 1.42-1.48 (1H, m), 1.54-1.62 (4H, m), 1.82-1.90 (2H, m), 2.38-2.62 (3H, m), 2.68-2.76 (2H, m), 2.98-3.08 (3H, m), 3.72-3.77 (1H, m), 3.82 (2H, s), 4.13-4.18 (1H, m), 4.33 (1H, d, J 9.0), 6.48 (1H, s), 6.64 (1H, d, J 16.5), 7.12-7.18 (2H, m), 7.37-7.43 (2H, m), 7.45 (1H, d, J 16.5). extracted with ethyl acetate (3×20 ml) The organic extracts were washed with brine (50 ml) dried over MgSO4 concentrated in vacuo The residue was purified by flash chromatography eluting with ethyl acetate: hexane (1:4)

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

実験手順: A cooled (0° C.) solution of (rac)-4-(8-amino-5,6,7,8-tetrahydroisoquinolin-4-yl)benzonitrile (example 1) (62.3 mg, 250 μmol) in CH2Cl2 (3 ml) was treated with propylsulfamoyl chloride (98.5 mg, 625 μmol) in CH2Cl2 (0.6 ml) and Et3N (69.7 μL, 500 μmol). After 1 h the mixture was stirred at room temperature for 1 h, cooled down (0° C.) and treated again with Et3N (69.7 μL, 500 μmol). After ½ h at room temperature, the mixture was treated with MeOH (0.2 mL) and extracted with water/AcOEt (3×). The organic phases were dried over Na2SO4, filtered and evaporated under reduced pressure. Purification by flash chromatography (50 g SiO2, Telos-cartridge, CH2Cl2/MeOH (1 to 3%)) and precipitation from CH2Cl2 with n-pentane gave the title compound (63 mg, 68%) as off-white powder. MS: 371.2 (M+H+). cooled down (0° C.) After ½ h at room temperature extracted with water/AcOEt (3×) The organic phases were dried over Na2SO4 filtered evaporated under reduced pressure Purification by flash chromatography (50 g SiO2, Telos-cartridge, CH2Cl2/MeOH (1 to 3%)) and precipitation from CH2Cl2 with n-pentane

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

実験手順: A cooled (0° C.) solution of (rac)-4-(8-amino-5,6,7,8-tetrahydroisoquinolin-4-yl)benzonitrile (example 1) (62.3 mg, 250 μmol) in CH2Cl2 (3 ml) was treated with propylsulfamoyl chloride (98.5 mg, 625 μmol) in CH2Cl2 (0.6 ml) and Et3N (69.7 μL, 500 μmol). After 1 h the mixture was stirred at room temperature for 1 h, cooled down (0° C.) and treated again with Et3N (69.7 μL, 500 μmol). After ½ h at room temperature, the mixture was treated with MeOH (0.2 mL) and extracted with water/AcOEt (3×). The organic phases were dried over Na2SO4, filtered and evaporated under reduced pressure. Purification by flash chromatography (50 g SiO2, Telos-cartridge, CH2Cl2/MeOH (1 to 3%)) and precipitation from CH2Cl2 with n-pentane gave the title compound (63 mg, 68%) as off-white powder. MS: 371.2 (M+H+). cooled down (0° C.) After ½ h at room temperature extracted with water/AcOEt (3×) The organic phases were dried over Na2SO4 filtered evaporated under reduced pressure Purification by flash chromatography (50 g SiO2, Telos-cartridge, CH2Cl2/MeOH (1 to 3%)) and precipitation from CH2Cl2 with n-pentane

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

実験手順: A mixture of the product from Step 6 (100 mg, 0.27 mmol), triethylamine (110 mg, 1.1 mmol) and propylsulfamoyl chloride (170 mg, 1.1 mmol) in DCM (5 ml) was stirred at ambient temperature for 18 hrs. The reaction mixture was diluted with water (20 ml) and extracted with ethyl acetate (3×20 ml). The organic extracts were washed with brine (50 ml), dried over MgSO4 and concentrated in vacuo. The residue was purified by flash chromatography eluting with ethyl acetate: hexane (1:4) to afford N-(3-chloro-4-{(E)-2-[5-(4-fluorophenyl)-1-methyl-1H-pyrazol-3-yl]vinyl}bicyclo[4.2.1]non-3-en-9-yl)-N-propylsulfamide (98 mg, 74%). δH (400 MHz, CDCl3) 0.98 (3H, t, J 7.5), 1.42-1.48 (1H, m), 1.54-1.62 (4H, m), 1.82-1.90 (2H, m), 2.38-2.62 (3H, m), 2.68-2.76 (2H, m), 2.98-3.08 (3H, m), 3.72-3.77 (1H, m), 3.82 (2H, s), 4.13-4.18 (1H, m), 4.33 (1H, d, J 9.0), 6.48 (1H, s), 6.64 (1H, d, J 16.5), 7.12-7.18 (2H, m), 7.37-7.43 (2H, m), 7.45 (1H, d, J 16.5). extracted with ethyl acetate (3×20 ml) The organic extracts were washed with brine (50 ml) dried over MgSO4 concentrated in vacuo The residue was purified by flash chromatography eluting with ethyl acetate: hexane (1:4)

反応条件: temp:0.00; pressure:0.00; stir:

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: Propylsulfamoyl chloride (0.379 mL, 2.40 mmol) was added to methyl 3-amino-2,6-difluorobenzoate (0.150 mL, 0.802 mmol), TEA (0.335 mL, 2.40 mmol) in DCM (1.5 mL) at 0° C. The solution was allowed to warm to room temperature overnight. The solids were filtered, and the supernate was concentrated to provide crude methyl 2,6-difluoro-3-(N-propylsulfamoylamino)benzoate, which was used directly in next step. The solids were filtered the supernate was concentrated

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

実験手順: Propylsulfamoyl chloride (0.379 mL, 2.40 mmol) was added to methyl 3-amino-2,6-difluorobenzoate (0.150 mL, 0.802 mmol), TEA (0.335 mL, 2.40 mmol) in DCM (1.5 mL) at 0° C. The solution was warmed to room temperature overnight. The solids were filtered, and the supernate was concentrated to provide crude methyl 2,6-difluoro-3-(N-propylsulfamoylamino)benzoate, which was used directly in next step. The solids were filtered the supernate was concentrated