4-fluorobenzenesulfonamide

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:

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

Procedure: Following the general procedure of EXAMPLE 49 and making non-critical variations 2-(isochroman-1-yl)ethanol-O-methanesulfonate (LXXX, 0.412 g) and 4-(3,5-dimethylpiperazin-1-yl)benzenesulfonamide [(IV), 0.433 g; prepared from 4-fluorobenzenesulfonamide, III, and cis-2,6-dimethylpiperazine, II (Aldrich), by the method of EXAMPLE 47] gives the title compound; mp 170-175 (decomp)°; MS (m/z) 429; IR (mineral oil) 1153, 1596, 1325, 1162 and 1096 cm-1.

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

Procedure: To a solution of carbonyldiimidazole (13.2 mg, 0.081 mmol) and [4-(4,9-diethoxy-1-oxo-1,3-dihydro-2H-benzo[f]isoindol-2-yl)phenyl]acetic acid (30 mg, 0.074 mmol) in dichloromethane (2 ml) was added 4-fluorobenzenesulphonamide (14.3 mg, 0.081 mmol) and N,N-diisopropylethylamine (10.5 mg, 0.81 mmol). The mixture was stirred at ambient temperature under an atmosphere of nitrogen overnight. The reaction mixture was diluted with dichloromethane (3 ml) and then washed with 2N hydrochloric acid (5 ml). The organic phase was dried (MgSO4) and then concentrated in vacuo to give a brown gum. The residue was purified using mass directed autopurification to give the title compound as a white solid (14.7 mg, 35.3%). MH+563. washed with 2N hydrochloric acid (5 ml) The organic phase was dried (MgSO4) concentrated in vacuo to give a brown gum The residue was purified

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

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a cooled (ice-water bath) solution of 4-fluoro-benzenesulfonamide (320 mg, 1.83 mmol) in N,N-dimethylformamide (5 mL), was added sodium hydride (150 mg, 60% dispersion, 3.75 mmol) portion-wise. After the mixture was stirred at 0° C. for 10 minutes, a solution of 3,3-bis-bromomethyl-oxetane (440 mg, 1.8 mmol) in N,N-dimethylformamide (3 mL) was added. The resulting mixture was stirred at room temperature overnight, then neutralized with 1 N hydrochloric acid, and extracted with ethyl acetate (20 mL×3). The combined organic layers were washed with brine (20 mL×3), dried over sodium sulfate, and concentrated in vacuo. The residue was purified by flash column chromatography (elution with 20% ethyl acetate in petroleum ether) to afford 2-(4-fluoro-benzenesulfonyl)-2-aza-spiro[3.3]heptane (120 mg, 26%) as a white solid (reference: Blizzard T. A. et al., Bioorg. Med. Chem. Lett. 14 (2004) 3861-3864), MS cald, for C12H14FNO2S 255, obsd. (ESI+) [(M+H)+] 256. The resulting mixture was stirred at room temperature overnight extracted with ethyl acetate (20 mL×3) The combined organic layers were washed with brine (20 mL×3) dried over sodium sulfate concentrated in vacuo The residue was purified by flash column chromatography (elution with 20% ethyl acetate in petroleum ether)

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 2 of Example 18 from 2-[4-(2-ethyl-4-phenyl-1H-imidazol-1-yl)phenyl]ethylcarbamate and 4-fluorobenzenesulfonamide. MS (ESI) m/z 493 [M+H]+, 491 [M−H]−, 1H-NMR (CDCl3) δ 1.23 (3H, t, J=7.5 Hz), 2.68 (2H, q, J=7.7 Hz), 2.87 (2H, t, J=7.0 Hz), 3.42-3.60 (2H, m), 6.46 (1H, br), 7.16-7.28 (7H, m), 7.37 (2H, t, J=7.3 Hz), 7.76 2H, d, J=7.1 Hz), 7.85-7.91 (2H, m).

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 2 of Example 22 from phenyl 2-[4-(3,5-dimethyl-4-phenyl-1H-pyrazol-1-yl)phenyl]ethylcarbamate (step 1 of Example 22) and 4-fluorobenzenesulfonamide: 1H-NMR (CDCl3) δ 7.94-7.88 (2H, m), 7.47-7.15 (11H, m), 6.24 (1H, br.s), 3.48-3.42 (2H, m), 2.84 (2H, t, J=7.0 Hz), 2.32 (3H, s), 2.23 (3H, s).

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

Procedure: 4-Fluorobenzenesulfonamide (5.50 g, 31.4 mmoles) was dissolved in 100 ml of morpholine (99.6 g, 1.14 moles) and was refluxed for 3 days. The solvent was removed by evaporation, yielding an orange oil. Methylene chloride (100 ml) was added, causing the oil to solidify. The solid was collected by filtration, then heated in 100 ml of ethanol. After cooling, the solid was collected by filtration, yielding 5.59 g (73%) of 4-(4-morpholinyl)benzenesulfonamide as a white solid. was refluxed for 3 days The solvent was removed by evaporation yielding an orange oil The solid was collected by filtration heated in 100 ml of ethanol After cooling the solid was collected by filtration