2-bromo-N-tert-butylbenzenesulfonamide

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:90.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 2-Bromo-N-(tert-butyl)benzenesulfonamide (from Step B) (1.00 g, 3.92 mmol), p-tolyltrimethyltin (from Step C) (1.95 g, 6.67 mmol), bis(triphenylphosphinepalladium(II) chloride (Aldrich) (165 mg, 0.235 mmol) and dimethylformamide (25 ml) were heated with stirring under nitrogen at 90° C. for 5 hours. The black suspension was cooled to room temperature, then filtered through a pad of Celite which was washed with tetrahydrofuran. The colorless filtrate was evaporated to dryness, then chromatographed (silica gel, 10% ethyl acetate-hexane) to give the title compound (0.88 g, 74%) as a white solid; 1H NMR (300 MHz, CDCl3) δ8.16 (d, J=7.9 Hz, 1H), 7.60-7.37 (m, 4H), 7.36-7.24 (m, 3H), 3.57 (s, 1H), 2.42 (s, 3H), 0.99 (s, 9H). The black suspension was cooled to room temperature filtered through a pad of Celite which was washed with tetrahydrofuran The colorless filtrate was evaporated to dryness chromatographed (silica gel, 10% ethyl acetate-hexane)

Conditions: temp:90.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 2-Bromo-N-(tert-butyl)benzenesulfonamide (from Step B) (1.00 g, 3.92 mmol), p-tolyltrimethyltin (from Step C) (1.95 g, 6.67 mmol), bis(triphenylphosphinepalladium(II) chloride (Aldrich) (165 mg, 0.235 mmol) and dimethylformamide (25 ml) were heated with stirring under nitrogen at 90° C. for 5 hours. The black suspension was cooled to room temperature, then filtered through a pad of Celite which was washed with tetrahydrofuran. The colorless filtrate was evaporated to dryness, then chromatographed (silica gel, 10% ethyl acetate-hexane) to give the title compound (0.88 g, 74%) as a white solid; 1H NMR (300 MHz, CDCl3) δ8.16 (d, J=7.9 Hz, 1H), 7.60-7.37 (m, 4H), 7.36-7.24 (m, 3H), 3.57 (s, 1H), 2.42 (s, 3H), 0.99 (s, 9H). The black suspension was cooled to room temperature filtered through a pad of Celite which was washed with tetrahydrofuran The colorless filtrate was evaporated to dryness chromatographed (silica gel, 10% ethyl acetate-hexane)

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

Procedure: To a stirred solution of 2-bromobenzenesulfonyl chloride (Lancaster Synthesis) (2.21 g, 8.65 mmol) in chloroform (40 ml) under nitrogen at room temperature was added tert-butylamine (Aldrich) (2.30 ml, 21.9 mmol). The orange solution was stirred at room temperature for 12 hours, then the mixture evaporated to dryness. Flash chromatography (silica gel, 15% ethyl acetate-hexane) afforded the title compound, (2.12 g, 84%) as a white solid; 1H NMR (300 MHz, CDCl3) δ8.18 (d, J=8.5 Hz, 1H), 7.73 (d, J=8.5 Hz, 1H), 7.50-7.35 (m, 2H), 5.11 (s, 1H), 1.20 (s, 9H). the mixture evaporated to dryness

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

Procedure: To a stirred solution of 2-bromobenzenesulfonyl chloride (Lancaster Synthesis) (2.21 g, 8.65 mmol) in chloroform (40 ml) under nitrogen at room temperature was added tert-butylamine (Aldrich) (2.30 ml, 21.9 mmol). The orange solution was stirred at room temperature for 12 hours, then the mixture evaporated to dryness. Flash chromatography (silica gel, 15% ethyl acetate-hexane) afforded the title compound, (2.12 g, 84%) as a white solid; 1H NMR (300 MHz, CDCl3) δ8.18 (d, J=8.5 Hz, 1H), 7.73 (d, J=8.5 Hz, 1H), 7.50-7.35 (m, 2H), 5.11 (s, 1H), 1.20 (s, 9H). the mixture evaporated to dryness

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

Procedure: To a solution of 4.0 g (16 mmol) 2-bromobenzenesulfonyl chloride in 75 mL methylene chloride at 0° C. was added 3.7 mL (35 mmol) tert-butylamine. The mixture was allowed to warm to RT and stir for 1 hour. The mixture was poured into aqueous 5% HCl and extracted three times with ether. The combined organic material was dried over MgSO4, was stripped of solvent in vacuo, then was recrystallized from hexane/acetone to give 3.19 g (70% yield) of the title compound. Rf 0.17 in 10% EtOAc/hexane, visualized by UV; extracted three times with ether The combined organic material was dried over MgSO4 was recrystallized from hexane/acetone

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

Procedure: To a solution of 4.0 g (16 mmol) 2-bromobenzenesulfonyl chloride in 75 mL methylene chloride at 0° C. was added 3.7 mL (35 mmol) tert-butylamine. The mixture was allowed to warm to RT and stir for 1 hour. The mixture was poured into aqueous 5% HCl and extracted three times with ether. The combined organic material was dried over MgSO4, was stripped of solvent in vacuo, then was recrystallized from hexane/acetone to give 3.19 g (70% yield) of the title compound. Rf 0.17 in 10% EtOAc/hexane, visualized by UV; extracted three times with ether The combined organic material was dried over MgSO4 was recrystallized from hexane/acetone

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

Procedure: Compound 5-chloro-N-(((3S,3aS)-1-oxo-7-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1,3,3a,4-tetrahydrobenzo[b]oxazolo[3,4-d][1,4]oxazin-3-yl)methyl)thiophene-2-carboxamide (60 mg, 0.122 mmol) and N-t-butyl-o-bromobenzenesulfonamide (43 mg, 0.147 mmol) were dissolved in a mixed solvent of dioxane (5 ml) and water (0.5 ml). Cesium carbonate (80 mg, 0.245 mmol) was added, and tetrakis (triphenylphosphine) palladium (15 mg, 0.012 mmol) was added under the protection of Ar. The resulting mixture was allowed to react under agitation at 80° C. overnight. TLC (PE/EA=1/1) was employed to monitor the reaction. After the reaction completed, the mixture was filtered under reduced pressure, and the solvent was evaporated. Column chromatography (PE/EA=2/1) afforded off-white solid 25 mg, yield: 35.2%. to react under agitation at 80° C. overnight the reaction the mixture was filtered under reduced pressure the solvent was evaporated

Conditions: temp:90.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 2-Bromo-N-(tert-butyl)benzenesulfonamide (from Step A) (1.00 g, 3.92 mmol), p-tolyltrimethyltin (from Step B) (1.95 g, 6.67 mmol), bis(triphenylphosphine)palladium(II) chloride (Aldrich) (165 mg, 0.235 mmol) and dimethylformamide (25 ml) were heated with stirring under nitrogen at 90° C. for 5 hours. The black suspension was cooled to room temperature, then filtered through a pad of Celite which was washed with tetrahydrofuran. The colorless filtrate was evaporated to dryness then chromatographed (silica gel, 10% ethyl acetate-hexane) to give the title compound (0.88 g, 74%) as a white solid; 1H NMR (300 MHz, CDCl3) δ8.16 (d, J=7.9 Hz, 1H), 7.60-7.37 (m, 4H), 7.36-7.24 (m, 3H), 3.57 (s, 1H), 2.42 (s, 3H), 0.99 (s, 9H). The black suspension was cooled to room temperature filtered through a pad of Celite which was washed with tetrahydrofuran The colorless filtrate was evaporated to dryness then chromatographed (silica gel, 10% ethyl acetate-hexane)

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

Procedure: To a stirred solution of 2-bromobenzenesulfonyl chloride (Lancaster Synthesis) (2.21 g, 8.65 mmol) in chloroform (40 ml) under nitrogen at room temperature was added tert-butylamine (Aldrich) (2.30 ml, 21.9 mmol). The orange solution was stirred at room temperature for 12 hours, then the mixture evaporated to dryness. Flash chromatography (silica gel, 15% ethyl acetate-hexane) afforded the title compound (2.12 g, 84%) as a white solid; 1H NMR (300 MHz, CDCl3) δ8.18 (d, J=8.5 Hz, 1H), 7.73 (d, J=8.5 Hz, 1H), 7.50-7.35 (m, 2H), 5.11 (s, 1H), 1.20 (s, 9H). the mixture evaporated to dryness

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

Procedure: 2-Bromobenzenesulfonyl chloride (100.9 g, 394.9 mmol) was dissolved in DCM (500 mL, 8.0 mol) and cooled at 0° C. t-Butylamine (41.3 mL, 395 mmol) was added in 3 portions over approximately 1 minute. DIPEA (75.7 mL, 434 mmol) was immediately added in 3 portions over approximately 1 minute. The mixture was warmed to room temperature and stirred overnight. The product was washed with 1M H3PO4 (2×), with saturated. NaHCO3, and with saturated aqueous NaCl, then dried over MgSO4, filtered, and concentrated to yield 2-bromo-N-t-butyl-benzenesulfonamide (112 g) as a light brown solid. was added in 3 portions over approximately 1 minute The product was washed with 1M H3PO4 (2×) NaHCO3, and with saturated aqueous NaCl, then dried over MgSO4 filtered concentrated