2-bromo-N-[(4-methoxyphenyl)methyl]acetamide

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

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

Procedure: 220 mg of methyl 4-{[(3-chloro-2-methylphenyl)amino]sulfonyl}benzoate was dissolved in 1.10 mL of DMF, and 168 mg of 2-bromo-N-(4-methoxybenzyl)acetamide and 100 mg of potassium carbonate were added thereto, followed by stirring at room temperature for 7 hours. To the reaction liquid was added water, followed by extraction with ethyl acetate, and the organic layer was washed with brine, 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=7:3 to 4:6) to obtain 270 mg of methyl 4-[((3-chloro-2-methylphenyl)-{2-[(4-methoxybenzyl)amino]-2-oxoethyl}amino)sulfonyl]benzoate. The obtained methyl 4-[((3-chloro-2-methylphenyl)-{2-[(4-methoxybenzyl)amino]-2-oxoethyl}amino)sulfonyl]benzoate was dissolved in 2.00 mL of methanol and 1.50 mL of THF, and 1.05 mL of a 1 M aqueous sodium hydroxide solution was added thereto, followed by stirring at room temperature for 2 days. The reaction liquid was acidified by addition of 1 M hydrochloric acid, and then extracted with a mixed solvent of chloroform/methanol (5/1), and the organic layer was dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure, and the obtained residue was purified by silica gel chromatography (chloroform:methanol=100:0 to 90:10) to obtain 204 mg of 4-[((3-chloro-2-methylphenyl) {2-[(4-methoxybenzyl)amino]-2-oxoethyl}amino)sulfonyl]benzoic acid. To the reaction liquid followed by extraction with ethyl acetate the organic layer was washed with brine 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=7:3 to 4:6)

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

Procedure: 449 mg of N-(3-chloro-2-methylphenyl)-4-fluorobenzenesulfonamide was dissolved in 3.00 mL of DMF, and 387 mg of 2-bromo-N-(4-methoxybenzyl)acetamide and 207 mg of potassium carbonate were added thereto, followed by stirring at room temperature overnight. To the reaction liquid was added an aqueous sodium hydrogen carbonate solution, followed by extraction with chloroform, and the organic layer was washed with brine, 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) to obtain a product, which was crystallized from hexane/ethyl acetate to obtain 466 mg of N2-(3-chloro-2-methylphenyl)-N-(4-methoxybenzyl)-N2-[(4-fluorophenyl)sulfonyl]glycinamide. To the reaction liquid followed by extraction with chloroform the organic layer was washed with brine 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) to obtain a product, which was crystallized from hexane/ethyl acetate

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

Procedure: 449 mg of N-(3-chloro-2-methylphenyl)-4-fluorobenzenesulfonamide was dissolved in 3.00 mL of DMF, and 387 mg of 2-bromo-N-(4-methoxybenzyl)acetamide and 207 mg of potassium carbonate were added thereto, followed by stirring at room temperature overnight. To the reaction liquid was added an aqueous sodium hydrogen carbonate solution, followed by extraction with chloroform, and the organic layer was washed with brine, 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) to obtain a product, which was crystallized from hexane/ethyl acetate to obtain 466 mg of N2-(3-chloro-2-methylphenyl)-N-(4-methoxybenzyl)-N2-[(4-fluorophenyl)sulfonyl]glycinamide. To the reaction liquid followed by extraction with chloroform the organic layer was washed with brine 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) to obtain a product, which was crystallized from hexane/ethyl acetate

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

Procedure: 3.93 g of 3-chloro-2-methylaniline was dissolved in 10 mL of DMF, and 2.00 g of potassium carbonate was added thereto, followed by portionwise addition of 3.55 g of 2-bromo-N-(4-methoxybenzyl)acetamide over 1 hour. The mixture was stirred at room temperature overnight, and ice water was added thereto, followed by extraction with ethyl acetate. The organic layer was washed with brine, 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) to obtain 2.89 g of N2-(3-chloro-2-methylphenyl)-N-(4-methoxybenzyl)glycinamide. followed by extraction with ethyl acetate The organic layer was washed with brine 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)

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

Procedure: 3.93 g of 3-chloro-2-methylaniline was dissolved in 10 mL of DMF, and 2.00 g of potassium carbonate was added thereto, followed by portionwise addition of 3.55 g of 2-bromo-N-(4-methoxybenzyl)acetamide over 1 hour. The mixture was stirred at room temperature overnight, and ice water was added thereto, followed by extraction with ethyl acetate. The organic layer was washed with brine, 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) to obtain 2.89 g of N2-(3-chloro-2-methylphenyl)-N-(4-methoxybenzyl)glycinamide. followed by extraction with ethyl acetate The organic layer was washed with brine 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)

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

Procedure: 7.42 g of 4-methoxybenzylamine was dissolved in 70 mL of methylene chloride, and a solution (10 mL) of 23.2 g of bromoacetyl bromide in methylene chloride was added thereto at −10° C. To the reaction liquid was added dropwise a solution (10 mL) of 8.0 mL of triethylamine in methylene chloride at 0° C., followed by stirring at room temperature for 30 minutes. To the reaction liquid was added water under ice-cooling, followed by extraction with methylene chloride. The organic layer was washed with an aqueous saturated sodium hydrogen carbonate solution, and then dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure, and the obtained residue was purified by silica gel column chromatography (hexane:ethyl acetate=90:10 to 0:100) to obtain a product, which was recrystallized from ethyl acetate to obtain 6.11 g of 2-bromo-N-(4-methoxybenzyl)acetamide. at −10° C To the reaction liquid To the reaction liquid cooling followed by extraction with methylene chloride The organic layer was washed with an aqueous saturated sodium hydrogen carbonate solution dried over anhydrous magnesium sulfate The solvent was evaporated under reduced pressure the obtained residue was purified by silica gel column chromatography (hexane:ethyl acetate=90:10 to 0:100) to obtain a product, which was recrystallized from ethyl acetate

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

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

Procedure: 220 mg of methyl 4-{[(3-chloro-2-methylphenyl)amino]sulfonyl}benzoate was dissolved in 1.10 mL of DMF, and 168 mg of 2-bromo-N-(4-methoxybenzyl)acetamide and 100 mg of potassium carbonate were added thereto, followed by stirring at room temperature for 7 hours. To the reaction liquid was added water, followed by extraction with ethyl acetate, and the organic layer was washed with brine, 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=7:3 to 4:6) to obtain 270 mg of methyl 4-[((3-chloro-2-methylphenyl)-{2-[(4-methoxybenzyl)amino]-2-oxoethyl}amino)sulfonyl]benzoate. The obtained methyl 4-[((3-chloro-2-methylphenyl)-{2-[(4-methoxybenzyl)amino]-2-oxoethyl}amino)sulfonyl]benzoate was dissolved in 2.00 mL of methanol and 1.50 mL of THF, and 1.05 mL of a 1 M aqueous sodium hydroxide solution was added thereto, followed by stirring at room temperature for 2 days. The reaction liquid was acidified by addition of 1 M hydrochloric acid, and then extracted with a mixed solvent of chloroform/methanol (5/1), and the organic layer was dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure, and the obtained residue was purified by silica gel chromatography (chloroform:methanol=100:0 to 90:10) to obtain 204 mg of 4-[((3-chloro-2-methylphenyl) {2-[(4-methoxybenzyl)amino]-2-oxoethyl}amino)sulfonyl]benzoic acid. To the reaction liquid followed by extraction with ethyl acetate the organic layer was washed with brine 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=7:3 to 4:6)

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

Procedure: 449 mg of N-(3-chloro-2-methylphenyl)-4-fluorobenzenesulfonamide was dissolved in 3.00 mL of DMF, and 387 mg of 2-bromo-N-(4-methoxybenzyl)acetamide and 207 mg of potassium carbonate were added thereto, followed by stirring at room temperature overnight. To the reaction liquid was added an aqueous sodium hydrogen carbonate solution, followed by extraction with chloroform, and the organic layer was washed with brine, 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) to obtain a product, which was crystallized from hexane/ethyl acetate to obtain 466 mg of N2-(3-chloro-2-methylphenyl)-N-(4-methoxybenzyl)-N2-[(4-fluorophenyl)sulfonyl]glycinamide. To the reaction liquid followed by extraction with chloroform the organic layer was washed with brine 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) to obtain a product, which was crystallized from hexane/ethyl acetate

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

Procedure: 3.93 g of 3-chloro-2-methylaniline was dissolved in 10 mL of DMF, and 2.00 g of potassium carbonate was added thereto, followed by portionwise addition of 3.55 g of 2-bromo-N-(4-methoxybenzyl)acetamide over 1 hour. The mixture was stirred at room temperature overnight, and ice water was added thereto, followed by extraction with ethyl acetate. The organic layer was washed with brine, 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) to obtain 2.89 g of N2-(3-chloro-2-methylphenyl)-N-(4-methoxybenzyl)glycinamide. followed by extraction with ethyl acetate The organic layer was washed with brine 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)

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

Procedure: 7.42 g of 4-methoxybenzylamine was dissolved in 70 mL of methylene chloride, and a solution (10 mL) of 23.2 g of bromoacetyl bromide in methylene chloride was added thereto at −10° C. To the reaction liquid was added dropwise a solution (10 mL) of 8.0 mL of triethylamine in methylene chloride at 0° C., followed by stirring at room temperature for 30 minutes. To the reaction liquid was added water under ice-cooling, followed by extraction with methylene chloride. The organic layer was washed with an aqueous saturated sodium hydrogen carbonate solution, and then dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure, and the obtained residue was purified by silica gel column chromatography (hexane:ethyl acetate=90:10 to 0:100) to obtain a product, which was recrystallized from ethyl acetate to obtain 6.11 g of 2-bromo-N-(4-methoxybenzyl)acetamide. at −10° C To the reaction liquid To the reaction liquid cooling followed by extraction with methylene chloride The organic layer was washed with an aqueous saturated sodium hydrogen carbonate solution dried over anhydrous magnesium sulfate The solvent was evaporated under reduced pressure the obtained residue was purified by silica gel column chromatography (hexane:ethyl acetate=90:10 to 0:100) to obtain a product, which was recrystallized from ethyl acetate