N-methylbenzenesulfonamide

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:60.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of 5.1 g. (30 mmol) N-methylbenzenesulphonamide, 8.8 g. (33 mmol) ethyl 4-bromomethyl-cinnamate (m.p. 47° C.), 4.1 g. (30 mmol) potassium carbonate and 50 ml. dimethylformamide are heated, with stirring, for 4 days at 60° C. The reaction mixture is then cooled and stirred into cold water and the organic components extracted with diethyl ether. The ethereal solution is washed with 0.5 N aqueous sodium hydroxide solution, dried with anhydrous sodium sulphate and evaporated. The residue is recrystallized from isopropanol to give 7.9 g. (73% of theory) ethyl 4-(N-methylbenzenesulphonamidomethyl)-cinnamate; m.p. 112°-112.5° C. A mixture of 5.1 g The reaction mixture is then cooled the organic components extracted with diethyl ether The ethereal solution is washed with 0.5 N aqueous sodium hydroxide solution dried with anhydrous sodium sulphate evaporated The residue is recrystallized from isopropanol to give 7.9 g

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

Procedure: 1.71 g (0.01 mole) of N-methylbenzenesulfonamide was added to 0.58 g (0.012 mole) of 50% sodium hydride in 15 ml of dry N,N-dimethylformamide. The mixture was stirred at room temperature for 30 minutes to react them. To the resulting sodium salt was added 2.10 g (0.012 mole) of 2-chlorobenzoyl chloride, and the mixture was stirred at room temperature for 1 hour. The N,N-dimethyl formamide was distilled off under reduced pressure. Cold water was added, and the resulting oil layer was extracted with benzene. The benzene layer was dried over anhydrous magnesium sulfate, and concentrated to afford almost pure N-methyl-N-(2-chlorobenzoyl)benzenesulfonamide in a yield of 92%. For further purification, this compound was subjected to chromatography or high vacuum distillation. This compound is designated as compound No. 16 in Table 2, and its melting point and elemental analysis values are shown in Table 2. to react them the mixture was stirred at room temperature for 1 hour The N,N-dimethyl formamide was distilled off under reduced pressure Cold water was added the resulting oil layer was extracted with benzene The benzene layer was dried over anhydrous magnesium sulfate concentrated

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

Procedure: 2-(4-fluorophenyl)-N-methyl-5-(3-(methyhphenylsulfonyl)carbamoyl)phenyl)benzofuran-3-carboxamide. In a 1 dram vial with stir bar were combined 3-(2-(4-fluorophenyl)-3-(methylcarbamoyl)benzofuran-5-yl)benzoic acid (35 mg, 0.090 mmol), DMAP (33 mg, 0.27 mmol), EDC hydrochloride (26 mg, 0.14 mmol), and N-methylbenzenesulfonamide (50 μL, 0.26 mmol). 1,2-Dichloroethane (0.5 mL) and DMF (0.5 mL) were added, the vial was capped, and the reaction was stirred at r.t. overnight. The reaction was filtered, purified by prep HPLC, and concentrated on a speedvac to give 27 mg (55% yield) of the title compound as a white powder. 1H NMR (500 MHz, CDCl3) δ ppm 7.91-8.02 (m, 5 H) 7.75-7.82 (m, 2 H) 7.65 (t, J=7.48 Hz, 1 H) 7.47-7.60 (m, 6 H) 7.15-7.24 (m, 2 H) 5.91 (d, J=4.27 Hz, 1 H) 3.36 (s, 3 H) 3.04 (d, J=4.88 Hz, 3 H). LC/MS was performed by using Shimadzu-VP instrument with UV detection at 220 nm and Waters Micromass. LC/MS method: solvent A=10% CH3CN/90% H2O/0.1% TFA, Solvent B=90% CH3CN/10% H2O/0.1% TFA, start % B=0, final % B=100, gradient time=2 min, stop time=3 min, flow rate=4 ml/min, column: Sunfire C18 5 μm 4.6×50 mm; HPLC Rt=1.89 min, (ES+) m/z (MH+)=543. Analytical HPLC were performed using a Shimadzu-VP instrument with UV detection at 220 nm and 254 nm. Analytical HPLC method: solvent A=5% CH3OH/95% H2O/10 mM NH4HCO3, solvent B=95% CH3OH/5% H2O/10 mM NH4HCO3, start % B=10, final % B=100, gradient time=15 min, stop time=18 min, flow rate=1 ml/min. Column: Phenomenex Gemini C18, 4.6 mm, 3 μm, Rt=17.42 min, purity=92%; column: Waters Xbridge Phenyl 4.6×150 mm, 3.5 μm, Rt=17.86 min, purity >90%. the vial was capped the reaction was stirred at r.t. overnight The reaction was filtered purified by prep HPLC concentrated on a speedvac

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

Procedure: DIAD (9.0 mL, 45.9 mmol) was added dropwise over 10 min to a stirred solution of 1-phenyl-3-buten-1-ol (4.0 g, 27.0 mmol), PPh3 (10.6 g, 40.5 mmol) and N-methylphenylsulfonamide (6.0 g, 35.0 mmol) in THF (200 mL) under N2 and the resulting mixture was stirred at RT for 20 h. H2O (200 mL) and Et2O (200 mL) were added and separated. The organics were washed with brine (150 mL) and concentrated under reduced pressure while loading on to MgSO4. The mixture was then purified by column chromatography on silica eluting with 3% Et2O/iso-hexanes to yield the sulfonamide (6.45 g, 79%). 1H NMR (CDCl3, 360 MHz) δ 7.78 (2H, d, J=7.8 Hz), 7.53 (1H, t, J=7.8 Hz), 7.44 (2H, t, J=7.8 Hz), 7.30–7.18 (5H, m), 5.67–5.52 (1H, m), 5.20 (1H, t, J=7.8 Hz), 5.02 (1H, dd, J=17.1, 1.5 Hz), 4.93 (1H, dd, J=10.2, 1.3 Hz), 2.70 (1H, app. quintet, J=7.1 Hz), 2.65 (3H, s), 2.44 (1H, app. quintet, J=7.1 Hz). separated The organics were washed with brine (150 mL) concentrated under reduced pressure while loading on to MgSO4 The mixture was then purified by column chromatography on silica eluting with 3% Et2O/iso-hexanes

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

Procedure: DIAD (9.0 mL, 45.9 mmol) was added dropwise over 10 min to a stirred solution of 1-phenyl-3-buten-1-ol (4.0 g, 27.0 mmol), PPh3 (10.6 g, 40.5 mmol) and N-methylphenylsulfonamide (6.0 g, 35.0 mmol) in THF (200 mL) under N2 and the resulting mixture was stirred at RT for 20 h. H2O (200 mL) and Et2O (200 mL) were added and separated. The organics were washed with brine (150 mL) and concentrated under reduced pressure while loading on to MgSO4. The mixture was then purified by column chromatography on silica eluting with 3% Et2O/iso-hexanes to yield the sulfonamide (6.45 g, 79%). 1H NMR (CDCl3, 360 MHz) δ 7.78 (2H, d, J=7.8 Hz), 7.53 (1H, t, J=7.8 Hz), 7.44 (2H, t, J=7.8 Hz), 7.30–7.18 (5H, m), 5.67–5.52 (1H, m), 5.20 (1H, t, J=7.8 Hz), 5.02 (1H, dd, J=17.1, 1.5 Hz), 4.93 (1H, dd, J=10.2, 1.3 Hz), 2.70 (1H, app. quintet, J=7.1 Hz), 2.65 (3H, s), 2.44 (1H, app. quintet, J=7.1 Hz). separated The organics were washed with brine (150 mL) concentrated under reduced pressure while loading on to MgSO4 The mixture was then purified by column chromatography on silica eluting with 3% Et2O/iso-hexanes

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

Procedure: In a 1 dram vial with stir bar were combined 3-(2-(4-fluorophenyl)-3-(methylcarbamoyl)benzofuran-5-yl)benzoic acid (35 mg, 0.090 mmol), DMAP (33 mg, 0.27 mmol), EDC hydrochloride (26 mg, 0.14 mmol), and N-methylbenzenesulfonamide (50 μL, 0.26 mmol). 1,2-Dichloroethane (0.5 mL) and DMF (0.5 mL) were added, the vial was capped, and the reaction was stirred at r.t. overnight. The reaction was filtered, purified by prep HPLC, and concentrated on a SPEEDVAC® to give 27 mg (55% yield) of the title compound as a white powder. 1H NMR (500 MHz, CDCl3) δ ppm 7.91-8.02 (m, 5H) 7.75-7.82 (m, 2H) 7.65 (t, J=7.48 Hz, 1H) 7.47-7.60 (m, 6H) 7.15-7.24 (m, 2H) 5.91 (d, J=4.27 Hz, 1H) 3.36 (s, 3H) 3.04 (d, J=4.88 Hz, 3H). LC/MS was performed by using Shimadzu-VP instrument with UV detection at 220 nm and Waters MICROMASS®. LC/MS method: solvent A=10% CH3CN/90% H2O/0.1% TFA, Solvent B=90% CH3CN/10% H2O/0.1% TFA, start % B=0, final % B=100, gradient time=2 min, stop time=3 min, flow rate=4 ml/min, column: Sunfire C18 5 μm 4.6×50 mm; HPLC Rt=1.89 min, (ES+) m/z (MH+)=543. Analytical HPLC were performed using a Shimadzu-VP instrument with UV detection at 220 nm and 254 nm. Analytical HPLC method: solvent A=5% CH3OH/95% H2O/10 mM NH4HCO3, solvent B=95% CH3OH/5% H2O/10 mM NH4HCO3, start % B=10, final % B=100, gradient time=15 min, stop time=18 min, flow rate=1 ml/min. Column: PHENOMENEX® Gemini C18, 4.6 mm, 3 μm, Rt=17.42 min, purity=92%; column: Waters XBridge phenyl 4.6×150 mm, 3.5 μm, Rt=17.86 min, purity>90%. the vial was capped the reaction was stirred at r.t. overnight The reaction was filtered purified by prep HPLC concentrated on a SPEEDVAC®

Conditions: temp:60.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of 5.1 g. (30 mmol) N-methylbenzenesulphonamide, 8.8 g. (33 mmol) ethyl 4-bromomethyl-cinnamate (m.p. 47° C.), 4.1 g. (30 mmol) potassium carbonate and 50 ml. dimethylformamide are heated, with stirring, for 4 days at 60° C. The reaction mixture is then cooled and stirred into cold water and the organic components extracted with diethyl ether. The ethereal solution is washed with 0.5 N aqueous sodium hydroxide solution, dried with anhydrous sodium sulphate and evaporated. The residue is recrystallized from isopropanol to give 7.9 g. (73% of theory) ethyl 4-(N-methylbenzenesulphonamidomethyl)-cinnamate; m.p. 112°-112.5° C. A mixture of 5.1 g The reaction mixture is then cooled the organic components extracted with diethyl ether The ethereal solution is washed with 0.5 N aqueous sodium hydroxide solution dried with anhydrous sodium sulphate evaporated The residue is recrystallized from isopropanol to give 7.9 g

Conditions: temp:60.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of 5.1 g. (30 mmol) N-methylbenzenesulphonamide, 8.8 g. (33 mmol) ethyl 4-bromomethyl-cinnamate (m.p. 47° C.), 4.1 g. (30 mmol) potassium carbonate and 50 ml. dimethylformamide are heated, with stirring, for 4 days at 60° C. The reaction mixture is then cooled and stirred into cold water and the organic components extracted with diethyl ether. The ethereal solution is washed with 0.5 N aqueous sodium hydroxide solution, dried with anhydrous sodium sulphate and evaporated. The residue is recrystallized from isopropanol to give 7.9 g. (73% of theory) ethyl 4-(N-methylbenzenesulphonamidomethyl)-cinnamate; m.p. 112°-112.5° C. A mixture of 5.1 g The reaction mixture is then cooled the organic components extracted with diethyl ether The ethereal solution is washed with 0.5 N aqueous sodium hydroxide solution dried with anhydrous sodium sulphate evaporated The residue is recrystallized from isopropanol to give 7.9 g

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

Procedure: 1.71 g (0.01 mole) of N-methylbenzenesulfonamide was added to 0.58 g (0.012 mole) of 50% sodium hydride in 15 ml of dry N,N-dimethylformamide. The mixture was stirred at room temperature for 30 minutes to react them. To the resulting sodium salt was added 2.10 g (0.012 mole) of 2-chlorobenzoyl chloride, and the mixture was stirred at room temperature for 1 hour. The N,N-dimethyl formamide was distilled off under reduced pressure. Cold water was added, and the resulting oil layer was extracted with benzene. The benzene layer was dried over anhydrous magnesium sulfate, and concentrated to afford almost pure N-methyl-N-(2-chlorobenzoyl)benzenesulfonamide in a yield of 92%. For further purification, this compound was subjected to chromatography or high vacuum distillation. This compound is designated as compound No. 16 in Table 2, and its melting point and elemental analysis values are shown in Table 2. to react them the mixture was stirred at room temperature for 1 hour The N,N-dimethyl formamide was distilled off under reduced pressure Cold water was added the resulting oil layer was extracted with benzene The benzene layer was dried over anhydrous magnesium sulfate concentrated