4-hydroxybenzenesulfonamide

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

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

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

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

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

Procedure: 4-Hydroxyphenylsulfonamide (3.46 g, 20 mmol) is dissolved in DMF (40 mL) and treated with tert-butyl-dimethylsilylchloride (3.31 g, 22.0 mmol) and imidazole (1.50 g, 22.0 mmol) at room temperature. After 20 hr, the reaction mixture is diluted with EtOAc (100 mL) and washed with 1.0 N HCl (2×50 mL). The organic phase is dried (MgSO4), filtered, and concentrated to yield an oil. The crude oil is purified by Biotage column chromatography (40M SiO2 column, eluted at 75 mL/min with 1:1 hexanes:EtOAc). A white solid is obtained (4.24 g, 15.4 mmol, 77%). ESI-MS m/e 288.1 (M++H); mp 117–118° C.; 1H NMR (CDCl3) δ 7.78 (d, 2H), 6.89 (d, 2H), 4.86 (br s, 2H), 0.97 (s, 9H), 0.20 (s, 6H). washed with 1.0 N HCl (2×50 mL) The organic phase is dried (MgSO4) filtered concentrated to yield an oil The crude oil is purified by Biotage column chromatography (40M SiO2 column, eluted at 75 mL/min with 1:1 hexanes:EtOAc) A white solid is obtained (4.24 g, 15.4 mmol, 77%)

Conditions: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 200 mg of N2-(3-chloro-2-methylphenyl)-N-(4-methoxybenzyl)glycinamide was dissolved in 2.0 mL of pyridine, and a solution (2.0 mL) of 200 mg of 4-hydroxybenzenesulfonamide in dichloroethane was added thereto, followed by stirring at 80° C. overnight. The reaction liquid was concentrated under reduced pressure, to the residue was added water, followed by extraction with ethyl acetate, and the organic layer was washed with 1 M hydrochloric acid and water, and then dried over anhydrous sodium sulfate. The solvent was evaporated under reduced pressure, and the obtained residue was purified by silica gel column chromatography (hexane:ethyl acetate=70:30 to 30:70), and further purified by silica gel column chromatography (chloroform:methanol=100:0 to 97:3), and the obtained residue was crystallized from diisopropyl ether to obtain 68 mg of N2-(3-chloro-2-methylphenyl)-N2-[(4-hydroxyphenyl)sulfonyl]-N-(4-methoxybenzyl)glycinamide. The reaction liquid was concentrated under reduced pressure, to the residue was added water followed by extraction with ethyl acetate the organic layer was washed with 1 M hydrochloric acid and water dried over anhydrous sodium sulfate The solvent was evaporated under reduced pressure the obtained residue was purified by silica gel column chromatography (hexane:ethyl acetate=70:30 to 30:70) further purified by silica gel column chromatography (chloroform:methanol=100:0 to 97:3) the obtained residue was crystallized from diisopropyl ether

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

Procedure: A mixture of phenyl 2-[4-(3,5-dimethyl-4-phenyl-1H-pyrazol-1-yl)phenyl]ethylcarbamate (step 1 of Example 22, 100 mg, 0.24 mmol), 4-hydroxybenzenesulfonamide (42 mg, 0.24 mmol), acetonitrile (3 mL) and 1,8-[5.4.0]-7-undecene (36 μL, 0.24 mmol) was stirred at room temperature for 16 h. The mixture was diluted with dichloromethane, and washed with 1 M hydrochloric acid and sat. NaHCO3 aq. The organic fraction was dried over MgSO4 and concentrated under reduced pressure. The residue was purified by TLC with dichloromethane/methanol (10:1) to afford 89 mg (74%) of the title compound as white solids: 1H-NMR [CDCl3/CD3OD(4:1)] δ 7.73-7.68 (2H, m), 7.48-7.23 (9H, m), 6.88-6.83 (2H, m), 3.47 (2H, t, J=6.7 Hz), 2.84 (2H, t, J=6.7 Hz), 2.33 (3H, s), 2.26 (3H, s). washed with 1 M hydrochloric acid and sat. NaHCO3 aq. The organic fraction was dried over MgSO4 concentrated under reduced pressure The residue was purified by TLC with dichloromethane/methanol (10:1)

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

Procedure: A mixture of phenyl 2-[4-(3,5-dimethyl-4-phenyl-1H-pyrazol-1-yl)phenyl]ethylcarbamate (step 1 of Example 22, 100 mg, 0.24 mmol), 4-hydroxybenzenesulfonamide (42 mg, 0.24 mmol), acetonitrile (3 mL) and 1,8-[5.4.0]-7-undecene (36 μL, 0.24 mmol) was stirred at room temperature for 16 h. The mixture was diluted with dichloromethane, and washed with 1 M hydrochloric acid and sat. NaHCO3 aq. The organic fraction was dried over MgSO4 and concentrated under reduced pressure. The residue was purified by TLC with dichloromethane/methanol (10:1) to afford 89 mg (74%) of the title compound as white solids: 1H-NMR [CDCl3/CD3OD(4:1)] δ 7.73-7.68 (2H, m), 7.48-7.23 (9H, m), 6.88-6.83 (2H, m), 3.47 (2H, t, J=6.7 Hz), 2.84 (2H, t, J=6.7 Hz), 2.33 (3H, s), 2.26 (3H, s). washed with 1 M hydrochloric acid and sat. NaHCO3 aq. The organic fraction was dried over MgSO4 concentrated under reduced pressure The residue was purified by TLC with dichloromethane/methanol (10:1)

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

Procedure: 4-Hydroxyphenylsulfonamide (3.46 g, 20 mmol) is dissolved in DMF (40 mL) and treated with tert-butyl-dimethylsilylchloride (3.31 g, 22.0 mmol) and imidazole (1.50 g, 22.0 mmol) at room temperature. After 20 hr, the reaction mixture is diluted with EtOAc (100 mL) and washed with 1.0 N HCl (2×50 mL). The organic phase is dried (MgSO4), filtered, and concentrated to yield an oil. The crude oil is purified by Biotage column chromatography (40M SiO2 column, eluted at 75 mL/min with 1:1 hexanes:EtOAc). A white solid is obtained (4.24 g, 15.4 mmol, 77%). ESI-MS m/e 288.1 (M++H); mp 117–118° C.; 1H NMR (CDCl3) δ 7.78 (d, 2H), 6.89 (d, 2H), 4.86 (br s, 2H), 0.97 (s, 9H), 0.20 (s, 6H). washed with 1.0 N HCl (2×50 mL) The organic phase is dried (MgSO4) filtered concentrated to yield an oil The crude oil is purified by Biotage column chromatography (40M SiO2 column, eluted at 75 mL/min with 1:1 hexanes:EtOAc) A white solid is obtained (4.24 g, 15.4 mmol, 77%)

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

Procedure: Into a round bottom flask, there are introduced 2.86 g (10 mmoles) of 3-(1-adamantyl)-4-methoxybenzoic acid, 1.73 g (10 mmoles) of 4-hydroxybenzenesulfonamide and 50 ml of THF. There are added, successively, 2.1 g (10 mmoles) of 1,3-dicyclohexylcarbodiimide and then 1.22 (10 mmoles) of 4-dimethylaminopyridine. The medium is stirred at ambient temperature for 4 hours. The reaction medium is poured into water and extracted with ethyl ether. The organic phase is decanted, washed with water, dried on magnesium sulfate and evaporated. The resulting solid is purified by chromatography on a silica column eluted by a 60:40 mixture of ethyl ether and hexane. After evaporation of the solvents, 2 g (46% yield) of 4-[3-(1-adamantyl)-4-methoxybenzoyloxy]benzenesulfonamide having a melting point of 223°-224° C. are recovered. There are added extracted with ethyl ether The organic phase is decanted washed with water dried on magnesium sulfate evaporated The resulting solid is purified by chromatography on a silica column eluted by a 60:40 mixture of ethyl ether and hexane

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

Procedure: To a solution of 4-hydroxybenzenesulfonamide (200 mg, 1.15 mmol) in ethanol (1 mL) was added potassium hydroxide solution (0.5M in ethanol, 2.5 mL). The mixture was stirred at room temperature for 1 hour and concentrated under reduced pressure to give the title compound as a pale orange crystal (quantitative yield). concentrated under reduced pressure

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