4-hydroxy-N,N-dimethylbenzenesulfonamide

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

実験手順: A two-phase mixture of 4-hydroxy-N,N-dimethyl-benzenesulfonamide (13 g), 3-chloro-3-methyl-1-butyne (33 g), tetra-n-butylammonium hydrogen sulfate (22 g), and sodium hydroxide (21 g) in a mixture of dichloromethane (195 ml) and water (97.5 ml) was vigorously stirred at room temperature for 48 hours. The organic layer was separated, washed with water and brine, dried over anhydrous magnesium sulfate, and concentrated. The residue was added to n-hexane and pulverized to give N,N-dimethyl-4-(1,1-dimethyl-2-propynyloxy)benzenesulfonamide (6.4 g). The organic layer was separated washed with water and brine dried over anhydrous magnesium sulfate concentrated The residue was added to n-hexane

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

実験手順: A two-phase mixture of 4-hydroxy-N,N-dimethyl-benzenesulfonamide (13 g), 3-chloro-3-methyl-1-butyne (33 g), tetra-n-butylammonium hydrogen sulfate (22 g), and sodium hydroxide (21 g) in a mixture of dichloromethane (195 ml) and water (97.5 ml) was vigorously stirred at room temperature for 48 hours. The organic layer was separated, washed with water and brine, dried over anhydrous magnesium sulfate, and concentrated. The residue was added to n-hexane and pulverized to give N,N-dimethyl-4-(1,1-dimethyl-2-propynyloxy)benzenesulfonamide (6.4 g). The organic layer was separated washed with water and brine dried over anhydrous magnesium sulfate concentrated The residue was added to n-hexane

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

実験手順: A mixture of 4-methoxy-N,N-dimethylbenzenesulfonamide (37 g) and aluminum chloride (69 g) in benzene (170 ml) was stirred under reflux for 30 minutes. The reaction mixture was poured into ice-water and extracted with ethyl acetate. The combined organic layers were washed with water and brine, dried over anhydrous magnesium sulfate, and concentrated. The residue was purified by recrystallization from toluene to give 4-hydroxy-N,N-dimethylbenzenesulfonamide (26 g). under reflux for 30 minutes extracted with ethyl acetate The combined organic layers were washed with water and brine dried over anhydrous magnesium sulfate concentrated The residue was purified by recrystallization from toluene

反応条件: temp:60.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution of 6.60 g (0.0330 mole) of N,N-dimethyl-4-hydroxybenzenesulfonamide dissolved in 150 ml of DMSO was added 1.32 g (0.0330 mole) of NaOH. The mixture was heated at 60° C. for 10 minutes and 7.1 g (0.030 mole) of 4-fluorophenyl phenyl sulfone was added. The reaction mixture was heated at 100° C. for 3 hrs and at 125° C. for 3 hrs and cooled. The mixture was poured into a solution of 200 ml of 20% aqueous NaOH and 500 ml of water. The crystalline product was collected, washed well with water and dried, which gave 11.5 g (92% yield) of product. Recrystallization from aqueous DMSO followed by recrystallization from ethanol afforded purified N,N-dimethyl-4-(4-(phenylsulfonyl)phenoxy)benzenesulfonamide, mp 99°-100° C. The reaction mixture was heated at 100° C. for 3 hrs and at 125° C. for 3 hrs cooled The crystalline product was collected washed well with water dried

反応条件: temp:160.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A mixture of 4-hydroxy-N,N-dimethyl-benzenesulfonamide (ChemService Inc., West Chester, Pa., USA; 18 mg, 0.089 mmol), 4-(4-chloro-pyrazolo[3,4-d]pyrimidin-1-yl)-piperidine-1-carboxylic acid tert-butyl ester (Intermediate 19; 30 mg, 0.089 mmol), and potassium carbonate (27 mg, 0.196 mmol) in dimethylformamide (1 mL) was heated in a microwave oven at 160° C. for 10 min. Saturated sodium carbonate solution was added to the reaction mixture, and the mixture was then filtered through a pad of silica gel to remove the precipitate. The silica gel pad was washed with methanol and the solvents were evaporated from the filtrate. The residue was purified by HPLC to give 4-[4-(4-dimethylsulfamoyl-phenoxy)-pyrazolo[3,4-d]pyrimidin-1-yl]-piperidine-1-carboxylic acid tert-butyl ester (13 mg, 28%) as a white solid. Mass spectrum MH+=503. the mixture was then filtered through a pad of silica gel to remove the precipitate The silica gel pad was washed with methanol the solvents were evaporated from the filtrate The residue was purified by HPLC

反応条件: temp:60.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution of 6.60 g (0.0330 mole) of N,N-dimethyl-4-hydroxybenzenesulfonamide dissolved in 150 ml of DMSO was added 1.32 g (0.0330 mole) of NaOH. The mixture was heated at 60° C. for 10 minutes and 7.1 g (0.030 mole) of 4-fluorophenyl phenyl sulfone was added. The reaction mixture was heated at 100° C. for 3 hrs and at 125° C. for 3 hrs and cooled. The mixture was poured into a solution of 200 ml of 20% aqueous NaOH and 500 ml of water. The crystalline product was collected, washed well with water and dried, which gave 11.5 g (92% yield) of product. Recrystallization from aqueous DMSO followed by recrystallization from ethanol afforded purified N,N-dimethyl-4-(4-(phenylsulfonyl)phenoxy)benzenesulfonamide, mp 99°-100° C. The reaction mixture was heated at 100° C. for 3 hrs and at 125° C. for 3 hrs cooled The crystalline product was collected washed well with water dried

反応条件: temp:60.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution of 6.37 g (0.0317 moles) of N,N-dimethyl-4-hydroxybenzenesulfonamide in 150 ml of DMSO was added 1.27 g (0.0317 moles) of NaOH. The mixture was heated to 60° C. and 5.26 g (0.288 moles) of 2-chloro-5-nitrobenzonitrile added and the mixture heated at 75° C. for 21/2 hrs. The reaction mixture was cooled and poured into a solution of 400 ml of 2 N aqueous NaOH and 300 ml of water. The product was collected by filtration, washed well with water and dried to obtain 8.8 g of product (88% yield). Recrystallization from a mixture of ethanol and dimethylformamide afforded purified N,N-dimethyl-4-(2-cyano-4-nitrophenoxy)benzenesulfonamide, mp 221.5°-223° C. the mixture heated at 75° C. for 21/2 hrs The reaction mixture was cooled The product was collected by filtration washed well with water dried

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

実験手順: A two-phase mixture of 4-hydroxy-N,N-dimethyl-benzenesulfonamide (13 g), 3-chloro-3-methyl-1-butyne (33 g), tetra-n-butylammonium hydrogen sulfate (22 g), and sodium hydroxide (21 g) in a mixture of dichloromethane (195 ml) and water (97.5 ml) was vigorously stirred at room temperature for 48 hours. The organic layer was separated, washed with water and brine, dried over anhydrous magnesium sulfate, and concentrated. The residue was added to n-hexane and pulverized to give N,N-dimethyl-4-(1,1-dimethyl-2-propynyloxy)benzenesulfonamide (6.4 g). The organic layer was separated washed with water and brine dried over anhydrous magnesium sulfate concentrated The residue was added to n-hexane

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

実験手順: A mixture of 4-methoxy-N,N-dimethylbenzenesulfonamide (37 g) and aluminum chloride (69 g) in benzene (170 ml) was stirred under reflux for 30 minutes. The reaction mixture was poured into ice-water and extracted with ethyl acetate. The combined organic layers were washed with water and brine, dried over anhydrous magnesium sulfate, and concentrated. The residue was purified by recrystallization from toluene to give 4-hydroxy-N,N-dimethylbenzenesulfonamide (26 g). under reflux for 30 minutes extracted with ethyl acetate The combined organic layers were washed with water and brine dried over anhydrous magnesium sulfate concentrated The residue was purified by recrystallization from toluene