3-bromo-4-fluorobenzenesulfonamide

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

実験手順: Example 238a was prepared according to the procedure used for the preparation of Example 96a, substituting cyclopropylmethanamine for cyclohexanamine, and 3-bromo-4-fluorobenzenesulfonamide for Example 86a, respectively, to provide the title compound. Example 238a was prepared used for the preparation of Example 96a

反応条件: temp:120.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A solution of 3-bromo-4-fluorobenzenesulfonamide (400 mg, 1.6 mmol) and 2,4-difluorophenol (228 mg, 1.76 mmol) in DMSO (16 ml) was treated with cesium carbonate (1 g, 3.2 mmol). The resulting mixture was heated to 120° C. for 20 min by microwave irriadation (normal). The mixture was treated with water (100 ml) and extracted with EtOAc (3×50 ml). The combined organic extracts were washed with saturated bicarbonate solution (aq), dried over sodium sulfate, filtered and concentrated in vacuo to afford a tan solid. The solid was purified by silica gel chromatography (12 g ISCO, 30% EtOAc in hexanes 30 ml/min) to give the title compound (340 mg, 58%) as a tan solid LCMS (M−H)−=362. extracted with EtOAc (3×50 ml) The combined organic extracts were washed with saturated bicarbonate solution (aq) dried over sodium sulfate filtered concentrated in vacuo to afford a tan solid The solid was purified by silica gel chromatography (12 g ISCO, 30% EtOAc in hexanes 30 ml/min)

反応条件: temp:120.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A solution of 3-bromo-4-fluorobenzenesulfonamide (400 mg, 1.6 mmol) and 2,4-difluorophenol (228 mg, 1.76 mmol) in DMSO (16 ml) was treated with cesium carbonate (1 g, 3.2 mmol). The resulting mixture was heated to 120° C. for 20 min by microwave irriadation (normal). The mixture was treated with water (100 ml) and extracted with EtOAc (3×50 ml). The combined organic extracts were washed with saturated bicarbonate solution (aq), dried over sodium sulfate, filtered and concentrated in vacuo to afford a tan solid. The solid was purified by silica gel chromatography (12 g ISCO, 30% EtOAc in hexanes 30 ml/min) to give the title compound (340 mg, 58%) as a tan solid LCMS (M−H)−=362. extracted with EtOAc (3×50 ml) The combined organic extracts were washed with saturated bicarbonate solution (aq) dried over sodium sulfate filtered concentrated in vacuo to afford a tan solid The solid was purified by silica gel chromatography (12 g ISCO, 30% EtOAc in hexanes 30 ml/min)

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

実験手順: A solution of 3-bromo-4-fluorobenzenesulfonyl chloride (1 g, 3.3 mmol, 90% pure) stirred at 0° C. in THF (15 ml) and DCM (5 ml) was treated with aqueous ammonium hydroxide (28%) by dropwise addition over 15 min. After stirring at 0° C. for 210 min, the mixture was acidified (pH=1) by addition of 1 N HCl (aq). After the mixture was concentrated in vacuo to near dryness, it was treated with water (50 ml), sonicated for 3 min and filtered. After the filter cake was washed sequentially with water (50 ml) and hexanes (100 ml), it was dried in vacuo to afford the title compound (503 mg, 60%) as a white solid which was carried forward without purification. LCMS (M−H)−=253. After the mixture was concentrated in vacuo was treated with water (50 ml) sonicated for 3 min filtered After the filter cake was washed sequentially with water (50 ml) and hexanes (100 ml), it was dried in vacuo

反応条件: temp:120.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A solution of 3-bromo-4-fluorobenzenesulfonamide (400 mg, 1.6 mmol) and 2,4-difluorophenol (228 mg, 1.76 mmol) in DMSO (16 ml) was treated with cesium carbonate (1 g, 3.2 mmol). The resulting mixture was heated to 120° C. for 20 min by microwave irridation (normal). The mixture was treated with water (100 ml) and extracted with EtOAc (3×50 ml). The combined organic extracts were washed with saturated bicarbonate solution (aq), dried over sodium sulfate, filtered and concentrated in vacuo to afford a tan solid. The solid was purified by silica gel chromatography (12 g ISCO, 30% EtOAc in hexanes 30 ml/min) to give the title compound (340 mg, 58%) as a tan solid LCMS (M−H)−=362. extracted with EtOAc (3×50 ml) The combined organic extracts were washed with saturated bicarbonate solution (aq) dried over sodium sulfate filtered concentrated in vacuo to afford a tan solid The solid was purified by silica gel chromatography (12 g ISCO, 30% EtOAc in hexanes 30 ml/min)

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

実験手順: A solution of 3-bromo-4-fluorobenzenesulfonyl chloride (1 g, 3.3 mmol, 90% pure) stirred at 0° C. in THF (15 ml) and DCM (5 ml) was treated with aqueous ammonium hydroxide (28%) by dropwise addition over 15 min. After stirring at 0° C. for 210 min, the mixture was acidified (pH=1) by addition of 1 N HCl (aq). After the mixture was concentrated in vacuo to near dryness, it was treated with water (50 ml), sonicated for 3 min and filtered. After the filter cake was washed sequentially with water (50 ml) and hexanes (100 ml), it was dried in vacuo to afford the title compound (503 mg, 60%) as a white solid which was carried forward without purification. LCMS (M−H)−=253. After the mixture was concentrated in vacuo was treated with water (50 ml) sonicated for 3 min filtered After the filter cake was washed sequentially with water (50 ml) and hexanes (100 ml), it was dried in vacuo

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

実験手順: A solution of 3-bromo-4-fluorobenzenesulfonyl chloride (1 g, 3.3 mmol, 90% pure) stirred at 0° C. in THF (15 ml) and DCM (5 ml) was treated with aqueous ammonium hydroxide (28%) by dropwise addition over 15 min. After stirring at 0° C. for 210 min, the mixture was acidified (pH=1) by addition of 1 N HCl (aq). After the mixture was concentrated in vacuo to near dryness, it was treated with water (50 ml), sonicated for 3 min and filtered. After the filter cake was washed sequentially with water (50 ml) and hexanes (100 ml), it was dried in vacuo to afford the title compound (503 mg, 60%) as a white solid which was carried forward without purification. LCMS (M−H)−=253. After the mixture was concentrated in vacuo was treated with water (50 ml) sonicated for 3 min filtered After the filter cake was washed sequentially with water (50 ml) and hexanes (100 ml), it was dried in vacuo

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

実験手順: Example 238a was prepared according to the procedure used for the preparation of Example 96a, substituting cyclopropylmethanamine for cyclohexanamine, and 3-bromo-4-fluorobenzenesulfonamide for Example 86a, respectively, to provide the title compound. Example 238a was prepared used for the preparation of Example 96a

反応条件: temp:120.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A solution of 3-bromo-4-fluorobenzenesulfonamide (400 mg, 1.6 mmol) and 2,4-difluorophenol (228 mg, 1.76 mmol) in DMSO (16 ml) was treated with cesium carbonate (1 g, 3.2 mmol). The resulting mixture was heated to 120° C. for 20 min by microwave irriadation (normal). The mixture was treated with water (100 ml) and extracted with EtOAc (3×50 ml). The combined organic extracts were washed with saturated bicarbonate solution (aq), dried over sodium sulfate, filtered and concentrated in vacuo to afford a tan solid. The solid was purified by silica gel chromatography (12 g ISCO, 30% EtOAc in hexanes 30 ml/min) to give the title compound (340 mg, 58%) as a tan solid LCMS (M−H)−=362. extracted with EtOAc (3×50 ml) The combined organic extracts were washed with saturated bicarbonate solution (aq) dried over sodium sulfate filtered concentrated in vacuo to afford a tan solid The solid was purified by silica gel chromatography (12 g ISCO, 30% EtOAc in hexanes 30 ml/min)

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

実験手順: A solution of 3-bromo-4-fluorobenzenesulfonyl chloride (1 g, 3.3 mmol, 90% pure) stirred at 0° C. in THF (15 ml) and DCM (5 ml) was treated with aqueous ammonium hydroxide (28%) by dropwise addition over 15 min. After stirring at 0° C. for 210 min, the mixture was acidified (pH=1) by addition of 1 N HCl (aq). After the mixture was concentrated in vacuo to near dryness, it was treated with water (50 ml), sonicated for 3 min and filtered. After the filter cake was washed sequentially with water (50 ml) and hexanes (100 ml), it was dried in vacuo to afford the title compound (503 mg, 60%) as a white solid which was carried forward without purification. LCMS (M−H)−=253. After the mixture was concentrated in vacuo was treated with water (50 ml) sonicated for 3 min filtered After the filter cake was washed sequentially with water (50 ml) and hexanes (100 ml), it was dried in vacuo

反応条件: temp:120.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A solution of 3-bromo-4-fluorobenzenesulfonamide (400 mg, 1.6 mmol) and 2,4-difluorophenol (228 mg, 1.76 mmol) in DMSO (16 ml) was treated with cesium carbonate (1 g, 3.2 mmol). The resulting mixture was heated to 120° C. for 20 min by microwave irridation (normal). The mixture was treated with water (100 ml) and extracted with EtOAc (3×50 ml). The combined organic extracts were washed with saturated bicarbonate solution (aq), dried over sodium sulfate, filtered and concentrated in vacuo to afford a tan solid. The solid was purified by silica gel chromatography (12 g ISCO, 30% EtOAc in hexanes 30 ml/min) to give the title compound (340 mg, 58%) as a tan solid LCMS (M−H)−=362. extracted with EtOAc (3×50 ml) The combined organic extracts were washed with saturated bicarbonate solution (aq) dried over sodium sulfate filtered concentrated in vacuo to afford a tan solid The solid was purified by silica gel chromatography (12 g ISCO, 30% EtOAc in hexanes 30 ml/min)

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

実験手順: A solution of 3-bromo-4-fluorobenzenesulfonyl chloride (1 g, 3.3 mmol, 90% pure) stirred at 0° C. in THF (15 ml) and DCM (5 ml) was treated with aqueous ammonium hydroxide (28%) by dropwise addition over 15 min. After stirring at 0° C. for 210 min, the mixture was acidified (pH=1) by addition of 1 N HCl (aq). After the mixture was concentrated in vacuo to near dryness, it was treated with water (50 ml), sonicated for 3 min and filtered. After the filter cake was washed sequentially with water (50 ml) and hexanes (100 ml), it was dried in vacuo to afford the title compound (503 mg, 60%) as a white solid which was carried forward without purification. LCMS (M−H)−=253. After the mixture was concentrated in vacuo was treated with water (50 ml) sonicated for 3 min filtered After the filter cake was washed sequentially with water (50 ml) and hexanes (100 ml), it was dried in vacuo