N-(二甲基氨磺酰基)-4-氟苯甲酰胺

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To a solution of 4-fluorobenzoic acid (700 mg, 5.0 mmol) in 1,2-dichloroethane (30 mL) was added EDCI (2.38 g, 12.5 mmol), DMAP (1.52 mg, 12.5 mmol) and N,N-diisopropylethylamine (2.17 mL, 12.5 mmol) and stirred for 20 minutes at room temperature. N,N-dimethylaminosulfonamide (1.24 g, 10.0 mmol) was added to the solution and the mixture heated at 60° C. for 2.5 hours. The mixture was cooled, diluted with water (20 mL) and 2M HCl (20 mL) and extracted with DCM (3×30 mL), washed with water (20 mL) and dried over MgSO4. The solvent was removed in vacuo to afford the title compound as a white solid (585 mg, 47%). No further purification was necessary. the mixture heated at 60° C. for 2.5 hours The mixture was cooled extracted with DCM (3×30 mL) washed with water (20 mL) dried over MgSO4 The solvent was removed in vacuo

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To a solution of 3,4-dichlorobenzyl alcohol (500 mg, 2.8 mmol) in THF (20 mL) was added sodium hydride (113 mg, 2.8 mmol, 60% dispersion in mineral oil) and stirred at room temperature for 2 hours and then at 50° C. for 30 minutes. Cooled to room temperature and the solvent removed in vacuo to afford an orange solid. This was dissolved in DMSO (5 mL) to which was added a solution of N-[(dimethylamino)sulfonyl]-4-fluorobenzamide (Preparation 11, 580 mg, 2.3 mmol) in DMSO (10 mL) slowly. The dark red solution was heated at 50° C. for 18 h then 120° C. for 2 hours. The mixture was cooled and poured onto water (50 mL) containing 2M HCl (30 mL) and extracted with EtOAc (2×30 mL), washed with 1M HCl (30 mL) and dried over MgSO4, filtered and solvent removed in vacuo to give 1.9 g of crude residue that was purified using reverse phase preparative HPLC to afford the title compound. at 50° C. for 30 minutes Cooled to room temperature the solvent removed in vacuo to afford an orange solid The dark red solution was heated at 50° C. for 18 h 120° C. for 2 hours The mixture was cooled poured onto water (50 mL) extracted with EtOAc (2×30 mL) washed with 1M HCl (30 mL) dried over MgSO4 filtered solvent removed in vacuo to give 1.9 g of crude residue that was purified