4-(bromomethyl)-1-fluoro-2-methylsulfonylbenzene

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: (Step 2) A solution of 2-amino-5-chloronicotinamide (685 mg) and 4-(bromomethyl)-1-fluoro-2-(methylsulfonyl)benzene obtained in Step 1 (1.6 g) in DMF (10 ml) was stirred at 90° C. for 24 hr. The mixture was allowed to cool to room temperature, methanol and ethyl acetate were added, and the precipitated crystals were collected by filtration. The obtained crystals were dissolved in 1N sodium hydroxide solution, and the solution was extracted with ethyl acetate. The organic layer was washed with saturated brine, and dried over magnesium sulfate. The solvent was evaporated under reduced pressure. The residue was purified by basic silica gel column chromatography (ethyl acetate:hexane=4:1). The obtained yellow solid was dissolved in methanol, 4N hydrogen chloride-ethyl acetate solution (2 ml) was added, and the precipitated crystals were collected by filtration, and recrystallized to give the title compound (510 mg). the precipitated crystals were collected by filtration The obtained crystals were dissolved in 1N sodium hydroxide solution the solution was extracted with ethyl acetate The organic layer was washed with saturated brine dried over magnesium sulfate The solvent was evaporated under reduced pressure The residue was purified by basic silica gel column chromatography (ethyl acetate:hexane=4:1) The obtained yellow solid was dissolved in methanol 4N hydrogen chloride-ethyl acetate solution (2 ml) was added the precipitated crystals were collected by filtration recrystallized

反応条件: temp:85.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: (Step 1) Triphenylphosphine (3.21 g) was suspended in acetonitrile (50 ml), bromine (0.64 ml) was added, and the mixture was stirred for 30 min. [4-Fluoro-3-(methylsulfonyl)phenyl]methanol (2.5 g) was added to the reaction mixture, and the mixture was stirred at 85° C. for 20 hr, treated with aqueous sodium hydrogen carbonate solution, and extracted with ethyl acetate. The extract was washed with saturated brine, and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure. The obtained residue was purified by basic silica gel chromatography (ethyl acetate:hexane=1:1) to give 4-(bromomethyl)-1-fluoro-2-(methylsulfonyl)benzene (1.64 g). was added to the reaction mixture extracted with ethyl acetate The extract was washed with saturated brine dried over anhydrous magnesium sulfate The solvent was evaporated under reduced pressure The obtained residue was purified by basic silica gel chromatography (ethyl acetate:hexane=1:1)

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: (Step 2) A solution of 2-amino-5-chloronicotinamide (685 mg) and 4-(bromomethyl)-1-fluoro-2-(methylsulfonyl)benzene obtained in Step 1 (1.6 g) in DMF (10 ml) was stirred at 90° C. for 24 hr. The mixture was allowed to cool to room temperature, methanol and ethyl acetate were added, and the precipitated crystals were collected by filtration. The obtained crystals were dissolved in 1N sodium hydroxide solution, and the solution was extracted with ethyl acetate. The organic layer was washed with saturated brine, and dried over magnesium sulfate. The solvent was evaporated under reduced pressure. The residue was purified by basic silica gel column chromatography (ethyl acetate:hexane=4:1). The obtained yellow solid was dissolved in methanol, 4N hydrogen chloride-ethyl acetate solution (2 ml) was added, and the precipitated crystals were collected by filtration, and recrystallized to give the title compound (510 mg). the precipitated crystals were collected by filtration The obtained crystals were dissolved in 1N sodium hydroxide solution the solution was extracted with ethyl acetate The organic layer was washed with saturated brine dried over magnesium sulfate The solvent was evaporated under reduced pressure The residue was purified by basic silica gel column chromatography (ethyl acetate:hexane=4:1) The obtained yellow solid was dissolved in methanol 4N hydrogen chloride-ethyl acetate solution (2 ml) was added the precipitated crystals were collected by filtration recrystallized

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: (Step 2) A solution of 2-amino-5-chloronicotinamide (685 mg) and 4-(bromomethyl)-1-fluoro-2-(methylsulfonyl)benzene obtained in Step 1 (1.6 g) in DMF (10 ml) was stirred at 90° C. for 24 hr. The mixture was allowed to cool to room temperature, methanol and ethyl acetate were added, and the precipitated crystals were collected by filtration. The obtained crystals were dissolved in 1N sodium hydroxide solution, and the solution was extracted with ethyl acetate. The organic layer was washed with saturated brine, and dried over magnesium sulfate. The solvent was evaporated under reduced pressure. The residue was purified by basic silica gel column chromatography (ethyl acetate:hexane=4:1). The obtained yellow solid was dissolved in methanol, 4N hydrogen chloride-ethyl acetate solution (2 ml) was added, and the precipitated crystals were collected by filtration, and recrystallized to give the title compound (510 mg). the precipitated crystals were collected by filtration The obtained crystals were dissolved in 1N sodium hydroxide solution the solution was extracted with ethyl acetate The organic layer was washed with saturated brine dried over magnesium sulfate The solvent was evaporated under reduced pressure The residue was purified by basic silica gel column chromatography (ethyl acetate:hexane=4:1) The obtained yellow solid was dissolved in methanol 4N hydrogen chloride-ethyl acetate solution (2 ml) was added the precipitated crystals were collected by filtration recrystallized

反応条件: temp:85.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: (Step 1) Triphenylphosphine (3.21 g) was suspended in acetonitrile (50 ml), bromine (0.64 ml) was added, and the mixture was stirred for 30 min. [4-Fluoro-3-(methylsulfonyl)phenyl]methanol (2.5 g) was added to the reaction mixture, and the mixture was stirred at 85° C. for 20 hr, treated with aqueous sodium hydrogen carbonate solution, and extracted with ethyl acetate. The extract was washed with saturated brine, and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure. The obtained residue was purified by basic silica gel chromatography (ethyl acetate:hexane=1:1) to give 4-(bromomethyl)-1-fluoro-2-(methylsulfonyl)benzene (1.64 g). was added to the reaction mixture extracted with ethyl acetate The extract was washed with saturated brine dried over anhydrous magnesium sulfate The solvent was evaporated under reduced pressure The obtained residue was purified by basic silica gel chromatography (ethyl acetate:hexane=1:1)

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: (Step 2) A solution of 2-amino-5-chloronicotinamide (685 mg) and 4-(bromomethyl)-1-fluoro-2-(methylsulfonyl)benzene obtained in Step 1 (1.6 g) in DMF (10 ml) was stirred at 90° C. for 24 hr. The mixture was allowed to cool to room temperature, methanol and ethyl acetate were added, and the precipitated crystals were collected by filtration. The obtained crystals were dissolved in 1N sodium hydroxide solution, and the solution was extracted with ethyl acetate. The organic layer was washed with saturated brine, and dried over magnesium sulfate. The solvent was evaporated under reduced pressure. The residue was purified by basic silica gel column chromatography (ethyl acetate:hexane=4:1). The obtained yellow solid was dissolved in methanol, 4N hydrogen chloride-ethyl acetate solution (2 ml) was added, and the precipitated crystals were collected by filtration, and recrystallized to give the title compound (510 mg). the precipitated crystals were collected by filtration The obtained crystals were dissolved in 1N sodium hydroxide solution the solution was extracted with ethyl acetate The organic layer was washed with saturated brine dried over magnesium sulfate The solvent was evaporated under reduced pressure The residue was purified by basic silica gel column chromatography (ethyl acetate:hexane=4:1) The obtained yellow solid was dissolved in methanol 4N hydrogen chloride-ethyl acetate solution (2 ml) was added the precipitated crystals were collected by filtration recrystallized

反応条件: temp:85.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: (Step 1) Triphenylphosphine (3.21 g) was suspended in acetonitrile (50 ml), bromine (0.64 ml) was added, and the mixture was stirred for 30 min. [4-Fluoro-3-(methylsulfonyl)phenyl]methanol (2.5 g) was added to the reaction mixture, and the mixture was stirred at 85° C. for 20 hr, treated with aqueous sodium hydrogen carbonate solution, and extracted with ethyl acetate. The extract was washed with saturated brine, and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure. The obtained residue was purified by basic silica gel chromatography (ethyl acetate:hexane=1:1) to give 4-(bromomethyl)-1-fluoro-2-(methylsulfonyl)benzene (1.64 g). was added to the reaction mixture extracted with ethyl acetate The extract was washed with saturated brine dried over anhydrous magnesium sulfate The solvent was evaporated under reduced pressure The obtained residue was purified by basic silica gel chromatography (ethyl acetate:hexane=1:1)

反応条件: temp:85.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: (Step 1) Triphenylphosphine (3.21 g) was suspended in acetonitrile (50 ml), bromine (0.64 ml) was added, and the mixture was stirred for 30 min. [4-Fluoro-3-(methylsulfonyl)phenyl]methanol (2.5 g) was added to the reaction mixture, and the mixture was stirred at 85° C. for 20 hr, treated with aqueous sodium hydrogen carbonate solution, and extracted with ethyl acetate. The extract was washed with saturated brine, and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure. The obtained residue was purified by basic silica gel chromatography (ethyl acetate:hexane=1:1) to give 4-(bromomethyl)-1-fluoro-2-(methylsulfonyl)benzene (1.64 g). was added to the reaction mixture extracted with ethyl acetate The extract was washed with saturated brine dried over anhydrous magnesium sulfate The solvent was evaporated under reduced pressure The obtained residue was purified by basic silica gel chromatography (ethyl acetate:hexane=1:1)

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: (Step 2) A solution of 2-amino-5-chloronicotinamide (685 mg) and 4-(bromomethyl)-1-fluoro-2-(methylsulfonyl)benzene obtained in Step 1 (1.6 g) in DMF (10 ml) was stirred at 90° C. for 24 hr. The mixture was allowed to cool to room temperature, methanol and ethyl acetate were added, and the precipitated crystals were collected by filtration. The obtained crystals were dissolved in 1N sodium hydroxide solution, and the solution was extracted with ethyl acetate. The organic layer was washed with saturated brine, and dried over magnesium sulfate. The solvent was evaporated under reduced pressure. The residue was purified by basic silica gel column chromatography (ethyl acetate:hexane=4:1). The obtained yellow solid was dissolved in methanol, 4N hydrogen chloride-ethyl acetate solution (2 ml) was added, and the precipitated crystals were collected by filtration, and recrystallized to give the title compound (510 mg). the precipitated crystals were collected by filtration The obtained crystals were dissolved in 1N sodium hydroxide solution the solution was extracted with ethyl acetate The organic layer was washed with saturated brine dried over magnesium sulfate The solvent was evaporated under reduced pressure The residue was purified by basic silica gel column chromatography (ethyl acetate:hexane=4:1) The obtained yellow solid was dissolved in methanol 4N hydrogen chloride-ethyl acetate solution (2 ml) was added the precipitated crystals were collected by filtration recrystallized

反応条件: temp:85.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: (Step 1) Triphenylphosphine (3.21 g) was suspended in acetonitrile (50 ml), bromine (0.64 ml) was added, and the mixture was stirred for 30 min. [4-Fluoro-3-(methylsulfonyl)phenyl]methanol (2.5 g) was added to the reaction mixture, and the mixture was stirred at 85° C. for 20 hr, treated with aqueous sodium hydrogen carbonate solution, and extracted with ethyl acetate. The extract was washed with saturated brine, and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure. The obtained residue was purified by basic silica gel chromatography (ethyl acetate:hexane=1:1) to give 4-(bromomethyl)-1-fluoro-2-(methylsulfonyl)benzene (1.64 g). 1H NMR (300 MHz, CDCl3) 8 ppm 3.24 (3H, s), 4.49 (2H, s), 7.19-7.31 (1H, m), 7.62-7.74 (1H, m), 7.99 (1H, dd, J=6.50, 2.35 Hz). was added to the reaction mixture extracted with ethyl acetate The extract was washed with saturated brine dried over anhydrous magnesium sulfate The solvent was evaporated under reduced pressure The obtained residue was purified by basic silica gel chromatography (ethyl acetate:hexane=1:1)

反応条件: temp:85.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: (Step 1) Triphenylphosphine (3.21 g) was suspended in acetonitrile (50 ml), bromine (0.64 ml) was added, and the mixture was stirred for 30 min. [4-Fluoro-3-(methylsulfonyl)phenyl]methanol (2.5 g) was added to the reaction mixture, and the mixture was stirred at 85° C. for 20 hr, treated with aqueous sodium hydrogen carbonate solution, and extracted with ethyl acetate. The extract was washed with saturated brine, and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure. The obtained residue was purified by basic silica gel chromatography (ethyl acetate:hexane=1:1) to give 4-(bromomethyl)-1-fluoro-2-(methylsulfonyl)benzene (1.64 g). 1H NMR (300 MHz, CDCl3) 8 ppm 3.24 (3H, s), 4.49 (2H, s), 7.19-7.31 (1H, m), 7.62-7.74 (1H, m), 7.99 (1H, dd, J=6.50, 2.35 Hz). was added to the reaction mixture extracted with ethyl acetate The extract was washed with saturated brine dried over anhydrous magnesium sulfate The solvent was evaporated under reduced pressure The obtained residue was purified by basic silica gel chromatography (ethyl acetate:hexane=1:1)

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: (Step 2) A solution of 2-amino-5-chloronicotinamide (685 mg) and 4-(bromomethyl)-1-fluoro-2-(methylsulfonyl)benzene obtained in Step 1 (1.6 g) in DMF (10 ml) was stirred at 90° C. for 24 hr. The mixture was allowed to cool to room temperature, methanol and ethyl acetate were added, and the precipitated crystals were collected by filtration. The obtained crystals were dissolved in 1N sodium hydroxide solution, and the solution was extracted with ethyl acetate. The organic layer was washed with saturated brine, and dried over magnesium sulfate. The solvent was evaporated under reduced pressure. The residue was purified by basic silica gel column chromatography (ethyl acetate:hexane=4:1). The obtained yellow solid was dissolved in methanol, 4N hydrogen chloride-ethyl acetate solution (2 ml) was added, and the precipitated crystals were collected by filtration, and recrystallized to give the title compound (510 mg). the precipitated crystals were collected by filtration The obtained crystals were dissolved in 1N sodium hydroxide solution the solution was extracted with ethyl acetate The organic layer was washed with saturated brine dried over magnesium sulfate The solvent was evaporated under reduced pressure The residue was purified by basic silica gel column chromatography (ethyl acetate:hexane=4:1) The obtained yellow solid was dissolved in methanol 4N hydrogen chloride-ethyl acetate solution (2 ml) was added the precipitated crystals were collected by filtration recrystallized