3-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:; See reaction.notes.procedure_details.

Procedure: The title compound was prepared according to the procedure described in step 1 of Example 42 from phenyl 2-{4-[5-methyl-4-phenyl-3-(trifluoromethyl)-1H-pyrazol-1-yl]phenyl}ethylcarbamate (step 7 of Example 52) and 3-hydroxybenzenesulfonamide: MS (ESI) m/z 545 [M+H]+, 543 [M−H]−, 1H-NMR (CDCl3) δ 7.48-7.01 (13H, m), 6.32 ▪ 1H, br.s), 3.50 (2H, t, J=6.1 Hz), 2.85 (2H, t, J=6.1 Hz), 2.20 (3H, s).

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

Procedure: The title compound was prepared according to the procedure described in step 1 of Example 42 from phenyl 2-{4-[5-methyl-4-phenyl-3-(trifluoromethyl)-1H-pyrazol-1-yl]phenyl}ethylcarbamate (step 7 of Example 52) and 3-hydroxybenzenesulfonamide: MS (ESI) m/z 545 [M+H]+, 543 [M−H]−, 1H-NMR (CDCl3) δ 7.48-7.01 (13H, m), 6.32 ▪ 1H, br.s), 3.50 (2H, t, J=6.1 Hz), 2.85 (2H, t, J=6.1 Hz), 2.20 (3H, s).

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

Procedure: The title compound was prepared according to the procedure described in step 1 of Example 42 from phenyl 2-[4-(3,5-dimethyl-4-phenyl-1H-pyrazol-1-yl)phenyl]ethylcarbamate (step 1 of Example 22) and 3-hydroxybenzenesulfonamide [Tetrahedron Lett., 1993, 34, 2043]: 1H-NMR (CDCl3) δ 7.49-7.20 (11H, m), 7.05-7.00 (1H, m), 6.56 (1H, br.s), 6.17 (1H, br.s), 3.59-3.52 (2H, m), 2.92 (2H, t, J=6.1 Hz), 2.36 (3H, s), 2.30 (3H, s).

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

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

Procedure: A solution of 3-hydroxybenzenesulfonamide (0.5 g, 2.89 mmol) and 1-(3-bromopropoxy)-4-phenoxy-2-propylbenzene (1.01 g, 2.89 mmol) with cesium carbonate (1.04 g, 3.18 mmol) in dry DMF (10 mL) was stirred at 50° C. for 5 h. The reaction suspension was cooled to room temperature and concentrated under vacuum to an orange residue. The residue was partitioned between ethyl acetate and water. The ethyl acetate phase was dried over sodium sulfate, filtered, and concentrated to an oil. The oil was chromatographed over silica gel with hexanes/ethyl acetate (2:1) to provide the title compound. concentrated under vacuum to an orange residue The residue was partitioned between ethyl acetate and water The ethyl acetate phase was dried over sodium sulfate filtered concentrated to an oil The oil was chromatographed over silica gel with hexanes/ethyl acetate (2:1)

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

Procedure: To a solution of 3-aminobenzenesulfonamide (2.35 g, 13.6 mmol) in 30% sulfuric acid (18 mL) stirred in a 0° C. ice-water bath was added dropwise a solution of sodium nitrite (1.22 g, 17.7 mmol) in water (10 mL). The resulting reaction solution continued to stir in an ice-water bath for 30 min. The solution was then stirred in a 100° C. oil bath for 30 min. After cooling to room temperature, the reaction solution was partitioned between ethyl acetate and brine. After shaking, the aqueous phase was extracted with ethyl acetate. The combined ethyl acetate phases were dried over sodium sulfate, filtered, and concentrated to a yellow solid (2.11 g, 89% yield). The resulting reaction solution The solution was then stirred in a 100° C. oil bath for 30 min the reaction solution was partitioned between ethyl acetate and brine After shaking the aqueous phase was extracted with ethyl acetate The combined ethyl acetate phases were dried over sodium sulfate filtered

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

Procedure: Following the Synthesis Method (B), 938 mg (5.42 mmol) of 3-hydroxybenzenesulfonamide was dissolved in 40 ml of tetrahydrofuran, then 892 μl (5.96 mmol) of 1,8-diazabicyclo[5,4,0]-7-undecene (hereinafter referred to as DBU) was added dropwise. The reaction solution was stirred at room temperature for 15 minutes, then 1.66 g (5.42 mmol) of methyl 4-chloro-2-N-phenoxycarbonylanthranilate was added and the mixture was stirred at room temperature overnight. An excess amount of water was poured into the reaction solution, then the mixture was made acidic with hydrochloric acid and extracted with ethyl acetate. The organic layer was washed with water and saturated saline, dried over anhydrous magnesium sulfate, and concentrated. The crude product thus obtained was purified by silica gel column chromatography (0% to 5% methanol/dichloromethane) to obtain 1.23 g (yield 59%) of methyl 4-chloro-2-{[(3-hydroxybenzenesulfonylamino)carbonyl]amino}benzoate. Properties: colorless amorphous, PMR (δ ppm, DMSO-d6): 3.91 (3H, s), 7.02 (1H, m), 7.09 (1H, m), 7.34 (1H, t), 7.57 (2H, m), 7.89 (1H, d), 8.38 (1H, d), 10.94 (1H, s). Next, the 1.23 g (3.2 mmol) of the compound thus obtained was dissolved in 20 ml of methanol, then 10 ml of 2N sodium hydroxide aqueous solution was added dropwise. The reaction solution was stirred at room temperature for 15 minutes, then an excess amount of water was added and the mixture was made acidic with hydrochloric acid. This was then stirred to cause crystals to precipitate which were then obtained by filtration and dried to obtain carboxylic acid. The product thus obtained was dissolved in 50 ml of tetrahydrofuran (hereinafter referred to as THF), then 434 mg (2.68 mmol) of CDI was added under ice cooling and the mixture was stirred for 30 minutes. The reaction solution was diluted with ethyl acetate, washed with water and saturated saline, and dried over anhydrous magnesium sulfate, then concentrated to obtain a crude product. The crude product was purified by silica gel column chromatography (ethyl acetate:n-hexane=1:2) to obtain 230 mg (yield 20%: 2 steps) of the above-identified compound. Properties: colorless crystal, Melting point: >200° C. (decomposition), PMR (δ ppm, DMSO-d6): 7.12 (2H, s), 7.24 (1H, d), 7.48 (1H, t), 7.58 (2H, s), 7.85 (1H, d), 10.28 (1H, s), 11.63 (1H, s). was added dropwise the mixture was stirred at room temperature overnight extracted with ethyl acetate The organic layer was washed with water and saturated saline dried over anhydrous magnesium sulfate concentrated The crude product thus obtained was purified by silica gel column chromatography (0% to 5% methanol/dichloromethane)

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

Procedure: The title compound was prepared according to the procedure described in step 1 of Example 42 from phenyl 2-{4-[5-methyl-4-phenyl-3-(trifluoromethyl)-1H-pyrazol-1-yl]phenyl}ethylcarbamate (step 7 of Example 52) and 3-hydroxybenzenesulfonamide: MS (ESI) m/z 545 [M+H]+, 543 [M−H]−, 1H-NMR (CDCl3) δ 7.48-7.01 (13H, m), 6.32 ▪ 1H, br.s), 3.50 (2H, t, J=6.1 Hz), 2.85 (2H, t, J=6.1 Hz), 2.20 (3H, s).

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

Procedure: The title compound was prepared according to the procedure described in step 1 of Example 42 from phenyl 2-[4-(3,5-dimethyl-4-phenyl-1H-pyrazol-1-yl)phenyl]ethylcarbamate (step 1 of Example 22) and 3-hydroxybenzenesulfonamide [Tetrahedron Lett., 1993, 34, 2043]: 1H-NMR (CDCl3) δ 7.49-7.20 (11H, m), 7.05-7.00 (1H, m), 6.56 (1H, br.s), 6.17 (1H, br.s), 3.59-3.52 (2H, m), 2.92 (2H, t, J=6.1 Hz), 2.36 (3H, s), 2.30 (3H, s).