4-(bromomethyl)-N,N-dimethylbenzenesulfonamide

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 4-(Bromomethyl)benzenesulfonyl chloride (5.0 g, 18.6 mmol) was dissolved in tetrahydrofuran. N,N-dimethylamine (7.7 mL, 15.5 mmol, 2M in tetrahydrofuran) and N,N-diisopropylethylamine (3.5 mL, 20.1 mmol) were added, and the reaction was allowed to stir at ambient temperature for 2 hours. The reaction was concentrated to an oil that was partitioned between water and ethyl acetate and extracted with ethyl acetate. The organic extracts were combined, washed with brine, dried over Na2SO4, and filtered. The resulting filtrate was concentrated to an oil which deposited needles that were a mixture of the title compound and 4-chloromethyl N,N-dimethylbenzenesulfonamide The resulting needles were collected and dried (2.3 g, 44%). ES-MS m/z 534 (M+H) and 578 (M+H). The reaction was concentrated to an oil that was partitioned between water and ethyl acetate extracted with ethyl acetate washed with brine dried over Na2SO4 filtered The resulting filtrate was concentrated to an oil which a mixture of the title compound and 4-chloromethyl N,N-dimethylbenzenesulfonamide The resulting needles were collected dried (2.3 g, 44%)

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 4-(Bromomethyl)benzenesulfonyl chloride (5.0 g, 18.6 mmol) was dissolved in tetrahydrofuran. N,N-dimethylamine (7.7 mL, 15.5 mmol, 2M in tetrahydrofuran) and and N,N-diisopropylethylamine (3.5 mL, 20.1 mmol) were added, and the reaction was allowed to stir at ambient temperature for 2 hours. The reaction was concentrated to an oil that was partitioned between water and ethyl acetate and extracted with ethyl acetate. The organic extracts were combined, washed with brine, dried over Na2SO4, and filtered. The resulting filtrate was concentrated to an oil which deposited needles that were a mixture of the title compound and 4-chloromethyl N,N-dimethylbenzenesulfonamide. The resulting needles were collected. and dried (2.3 g, 44%). ES-MS m/z 534 (M+H) and 578 (M+H) The reaction was concentrated to an oil that was partitioned between water and ethyl acetate extracted with ethyl acetate washed with brine dried over Na2SO4 filtered The resulting filtrate was concentrated to an oil which a mixture of the title compound and 4-chloromethyl N,N-dimethylbenzenesulfonamide The resulting needles were collected and dried (2.3 g, 44%)

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 6-bromo-7-methyl-1H-indole-2,3-dione (2.0 g, 8.33 mmol) in DMF (25 ml) was added potassium carbonate (2.3 g, 16.6 mmol). After stirring at this temperature for 30 minutes, was added 4-bromomethyl-N,N-dimethyl-benzenesulfonamide (3.0 g, 10.83 mmol). The reaction mixture was stirred at room temperature for six hours. It was then partitioned between water and ethyl acetate. The organic layer was dried over MgSO4, filtered and concentrated under vacuum to give the crude product which was chromatographed on flash silica gel eluting with 20% ethyl acetate in hexane, providing the title compound of 12A (0.392 g, 11% yield). The reaction mixture was stirred at room temperature for six hours It was then partitioned between water and ethyl acetate The organic layer was dried over MgSO4 filtered concentrated under vacuum to give the crude product which was chromatographed on flash silica gel eluting with 20% ethyl acetate in hexane

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 6-Bromo-2-oxo-1,2-dihydro-indole-3,3-dicarboxylic acid di-tert-butyl ester (5.10 g, 12.4 mmol) was dissolved in 40 ml of anhydrous N,N-dimethylformamide (DMF) under an atmosphere of dry N2. The solution was cooled to 0° C. after which time 60% sodium hydride in oil (500 mg, 12.4 mmol) was added and the solution was then stirred for 15 minutes at this temperature. The reaction mixture was the warmed to ambient temperature and stirred for 15 minutes after which time 4-bromomethyl-N,N-dimethyl-benzenesulfonamide (3.44 g, 12.4 mmol) was added. The mixture was stirred overnight after which time it was concentrated under vacuum and partitioned between DCM and water. The DCM layer was washed 3 more times with water, once with brine, dried over MgSO4, filtered and concentrated under vacuum to give 8.63 g of the titled compound as a yellow solid was added was added The mixture was stirred overnight after which time it was concentrated under vacuum partitioned between DCM and water The DCM layer was washed 3 more times with water once with brine, dried over MgSO4 filtered concentrated under vacuum