1-(4-fluorophenyl)-3-piperidin-4-ylurea

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

実験手順: To a solution of N-(piperidin-4-yl)-N′-(4-fluorophenyl)urea (0.3 g) in tetrahydrofuran (4 ml) were added in turn N,N-dimethylaminopyridine (0.23 g) and 4-fluorobenzenesulfonyl chloride (0.25 g) at 0° C. The mixture was allowed to warm to ambient temperature and stirred for 1 hour. The reaction mixture was taken up into a mixture of water and dichloromethane. The separated organic layer was washed in turn with hydrochloric acid (1N), aqueous sodium hydrogen carbonate, and brine, and dried over magnesium sulfate. Evaporation under reduced pressure gave a residue, which was triturated with diisopropyl ether to give N-(1-(4-fluorophenylsulfonyl)-piperidin-4-yl)-N′-(4-fluorophenyl)urea (0.468 g). The separated organic layer was washed in turn with hydrochloric acid (1N), aqueous sodium hydrogen carbonate, and brine dried over magnesium sulfate Evaporation under reduced pressure gave a residue, which was triturated with diisopropyl ether

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

実験手順: To a solution of N-(piperidin-4-yl)-N′-(4-fluorophenyl)urea (0.3 g) in tetrahydrofuran (4 ml) were added in turn pyridine (0.28 ml), methyl chloroformate (98 μl) and catalytic amount of N,N-dimethylaminopyridine at 0° C. The mixture was allowed to warm to ambient temperature and stirred for 2 hours. The reaction mixture was taken up into a mixture of water and ethyl acetate. The separated organic layer was washed in turn with hydrochloric acid (1N), aqueous sodium hydrogen carbonate, and brine, and dried over magnesium sulfate. Evaporation under reduced pressure gave a residue, which was triturated with diisopropyl ether to give N-(1-methoxycarbonylpiperidin-4-yl)-N′-(4-fluorophenyl)urea (0.312 g). The separated organic layer was washed in turn with hydrochloric acid (1N), aqueous sodium hydrogen carbonate, and brine dried over magnesium sulfate Evaporation under reduced pressure gave a residue, which was triturated with diisopropyl ether

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

実験手順: To a solution of N-(1-benzylpiperidin-4-yl)-N′-(4-fluorophenyl)urea (3.0 g) in a mixture of methanol (15 ml) and tetrahydrofuran (15 ml) was added palladium on carbon (10% w/w, 50% wet, 0.6 g), and the mixture was hydrogenated under atmospheric pressure of hydrogen for 8 hours. The catalyst was filtered off, and the solvents were evaporated under reduced pressure to give a residue, which was triturated with diisopropyl ether to give N-(piperidin-4-yl)-N′-(4-fluorophenyl)urea (1.97 g). The catalyst was filtered off the solvents were evaporated under reduced pressure to give a residue, which was triturated with diisopropyl ether

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

実験手順: To a solution of N-(piperidin-4-yl)-N′-(4-fluorophenyl)urea (0.3 g) in tetrahydrofuran (4 ml) were added in turn N,N-dimethylaminopyridine (0.23 g) and 4-fluorobenzenesulfonyl chloride (0.25 g) at 0° C. The mixture was allowed to warm to ambient temperature and stirred for 1 hour. The reaction mixture was taken up into a mixture of water and dichloromethane. The separated organic layer was washed in turn with hydrochloric acid (1N), aqueous sodium hydrogen carbonate, and brine, and dried over magnesium sulfate. Evaporation under reduced pressure gave a residue, which was triturated with diisopropyl ether to give N-(1-(4-fluorophenylsulfonyl)-piperidin-4-yl)-N′-(4-fluorophenyl)urea (0.468 g). The separated organic layer was washed in turn with hydrochloric acid (1N), aqueous sodium hydrogen carbonate, and brine dried over magnesium sulfate Evaporation under reduced pressure gave a residue, which was triturated with diisopropyl ether

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

実験手順: To a solution of N-(piperidin-4-yl)-N′-(4-fluorophenyl)urea (0.3 g) in tetrahydrofuran (4 ml) were added in turn pyridine (0.28 ml), methyl chloroformate (98 μl) and catalytic amount of N,N-dimethylaminopyridine at 0° C. The mixture was allowed to warm to ambient temperature and stirred for 2 hours. The reaction mixture was taken up into a mixture of water and ethyl acetate. The separated organic layer was washed in turn with hydrochloric acid (1N), aqueous sodium hydrogen carbonate, and brine, and dried over magnesium sulfate. Evaporation under reduced pressure gave a residue, which was triturated with diisopropyl ether to give N-(1-methoxycarbonylpiperidin-4-yl)-N′-(4-fluorophenyl)urea (0.312 g). The separated organic layer was washed in turn with hydrochloric acid (1N), aqueous sodium hydrogen carbonate, and brine dried over magnesium sulfate Evaporation under reduced pressure gave a residue, which was triturated with diisopropyl ether

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

実験手順: To a solution of N-(1-benzylpiperidin-4-yl)-N′-(4-fluorophenyl)urea (3.0 g) in a mixture of methanol (15 ml) and tetrahydrofuran (15 ml) was added palladium on carbon (10% w/w, 50% wet, 0.6 g), and the mixture was hydrogenated under atmospheric pressure of hydrogen for 8 hours. The catalyst was filtered off, and the solvents were evaporated under reduced pressure to give a residue, which was triturated with diisopropyl ether to give N-(piperidin-4-yl)-N′-(4-fluorophenyl)urea (1.97 g). The catalyst was filtered off the solvents were evaporated under reduced pressure to give a residue, which was triturated with diisopropyl ether

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

実験手順: To a solution of N-(piperidin-4-yl)-N′-(4-fluorophenyl)urea (0.3 g) in tetrahydrofuran (4 ml) were added in turn N,N-dimethylaminopyridine (0.23 g) and 4-fluorobenzenesulfonyl chloride (0.25 g) at 0° C. The mixture was allowed to warm to ambient temperature and stirred for 1 hour. The reaction mixture was taken up into a mixture of water and dichloromethane. The separated organic layer was washed in turn with hydrochloric acid (1N), aqueous sodium hydrogen carbonate, and brine, and dried over magnesium sulfate. Evaporation under reduced pressure gave a residue, which was triturated with diisopropyl ether to give N-(1-(4-fluorophenylsulfonyl)-piperidin-4-yl)-N′-(4-fluorophenyl)urea (0.468 g). The separated organic layer was washed in turn with hydrochloric acid (1N), aqueous sodium hydrogen carbonate, and brine dried over magnesium sulfate Evaporation under reduced pressure gave a residue, which was triturated with diisopropyl ether

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

実験手順: To a solution of N-(piperidin-4-yl)-N′-(4-fluorophenyl)urea (0.3 g) in tetrahydrofuran (4 ml) were added in turn pyridine (0.28 ml), methyl chloroformate (98 μl) and catalytic amount of N,N-dimethylaminopyridine at 0° C. The mixture was allowed to warm to ambient temperature and stirred for 2 hours. The reaction mixture was taken up into a mixture of water and ethyl acetate. The separated organic layer was washed in turn with hydrochloric acid (1N), aqueous sodium hydrogen carbonate, and brine, and dried over magnesium sulfate. Evaporation under reduced pressure gave a residue, which was triturated with diisopropyl ether to give N-(1-methoxycarbonylpiperidin-4-yl)-N′-(4-fluorophenyl)urea (0.312 g). The separated organic layer was washed in turn with hydrochloric acid (1N), aqueous sodium hydrogen carbonate, and brine dried over magnesium sulfate Evaporation under reduced pressure gave a residue, which was triturated with diisopropyl ether

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

実験手順: To a solution of N-(1-benzylpiperidin-4-yl)-N′-(4-fluorophenyl)urea (3.0 g) in a mixture of methanol (15 ml) and tetrahydrofuran (15 ml) was added palladium on carbon (10% w/w, 50% wet, 0.6 g), and the mixture was hydrogenated under atmospheric pressure of hydrogen for 8 hours. The catalyst was filtered off, and the solvents were evaporated under reduced pressure to give a residue, which was triturated with diisopropyl ether to give N-(piperidin-4-yl)-N′-(4-fluorophenyl)urea (1.97 g). The catalyst was filtered off the solvents were evaporated under reduced pressure to give a residue, which was triturated with diisopropyl ether