methyl benzenesulfonate

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: The 1-(2-bromoethyl)-4-hydroxymethylbenzene (0.5 g) is then added to a solution of 0.44 g methyl benzene-sulfonate and 0.32 g K2CO3 in 10 mL of methanol and allowed to react for 4 h. The solution is neutralized with methanolic HCl and extracted with ether. The ether extract is dried over Na2SO4, filtered, and the solvent removed under vacuum to yield 1-(methoxymethyl)-4-(2-bromoethyl)benzene (13). to react for 4 h extracted with ether The ether extract is dried over Na2SO4 filtered the solvent removed under vacuum

Conditions: temp:100.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 99 mg of 3-bromo-5-(2-pyridyl)-1-phenyl-1,2-dihydropyridin-2-one was dissolved in 10 ml of acetonitrile. 2 ml of methyl benzenesulfonate was added thereto, followed by stirring at 100° C. for 2 nights. After cooling to room temperature, the solvent was evaporated. The residue was dissolved in 10 ml of methanol, followed by cooled to 0° C. under stirring. Sodium borohydride was added 5 times at intervals of 5 hours, 1 g for each time, followed by further stirring at 0° C. overnight. Then the solvent was evaporated and a saturated aqueous solution of ammonium chloride was added to the residue, followed by extracting with ethyl acetate. The organic layer was washed with brine and dried over anhydrous magnesium sulfate. The solvent was evaporated, and the residue was purified by silica gel chromatography (hexane/ethyl acetate system), to give 107 mg of 3-bromo-5-(1-methyl-1,2,3,6-tetrahydropyridin-2-yl)-1-phenyl-1,2-dihydropyridin-2-one. The product was dissolved in 10 ml of dimethylformamide. 81 mg of 2-(2-cyanophenyl)-1,3,2-dioxaborinate, 142 mg of cesium carbonate and 7 mg of tetrakistriphenylphosphine palladium were added thereto, followed by stirring at 140° C. for 2 hours. After cooling to room temperature, water was added thereto, followed by extracting with ethyl acetate. The organic layer was washed with brine and dried over anhydrous magnesium sulfate. The solvent was evaporated, and the residue was purified by silica gel chromatography (hexane/ethyl acetate system), to give 41 mg of the title compound. After cooling to room temperature the solvent was evaporated The residue was dissolved in 10 ml of methanol by cooled to 0° C. under stirring Sodium borohydride was added 5 times at intervals of 5 hours, 1 g for each time by further stirring at 0° C. overnight Then the solvent was evaporated a saturated aqueous solution of ammonium chloride was added to the residue by extracting with ethyl acetate The organic layer was washed with brine dried over anhydrous magnesium sulfate The solvent was evaporated the residue was purified by silica gel chromatography (hexane/ethyl acetate system)

Conditions: temp:100.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 99 mg of 3-bromo-5-(2-pyridyl)-1-phenyl-1,2-dihydropyridin-2-one was dissolved in 10 ml of acetonitrile. 2 ml of methyl benzenesulfonate was added thereto, followed by stirring at 100° C. for 2 nights. After cooling to room temperature, the solvent was evaporated. The residue was dissolved in 10 ml of methanol, followed by cooled to 0° C. under stirring. Sodium borohydride was added 5 times at intervals of 5 hours, 1 g for each time, followed by further stirring at 0° C. overnight. Then the solvent was evaporated and a saturated aqueous solution of ammonium chloride was added to the residue, followed by extracting with ethyl acetate. The organic layer was washed with brine and dried over anhydrous magnesium sulfate. The solvent was evaporated, and the residue was purified by silica gel chromatography (hexane/ethyl acetate system), to give 107 mg of 3-bromo-5-(1-methyl-1,2,3,6-tetrahydropyridin-2-yl)-1-phenyl-1,2-dihydropyridin-2-one. The product was dissolved in 10 ml of dimethylformamide. 81 mg of 2-(2-cyanophenyl)-1,3,2-dioxaborinate, 142 mg of cesium carbonate and 7 mg of tetrakistriphenylphosphine palladium were added thereto, followed by stirring at 140° C. for 2 hours. After cooling to room temperature, water was added thereto, followed by extracting with ethyl acetate. The organic layer was washed with brine and dried over anhydrous magnesium sulfate. The solvent was evaporated, and the residue was purified by silica gel chromatography (hexane/ethyl acetate system), to give 41 mg of the title compound. After cooling to room temperature the solvent was evaporated The residue was dissolved in 10 ml of methanol by cooled to 0° C. under stirring Sodium borohydride was added 5 times at intervals of 5 hours, 1 g for each time by further stirring at 0° C. overnight Then the solvent was evaporated a saturated aqueous solution of ammonium chloride was added to the residue by extracting with ethyl acetate The organic layer was washed with brine dried over anhydrous magnesium sulfate The solvent was evaporated the residue was purified by silica gel chromatography (hexane/ethyl acetate system)

Conditions: temp:100.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 99 mg of 3-bromo-5-(2-pyridyl)-1-phenyl-1,2-dihydropyridin-2-one was dissolved in 10 ml of acetonitrile. 2 ml of methyl benzenesulfonate was added thereto, followed by stirring at 100° C. for 2 nights. After cooling to room temperature, the solvent was evaporated. The residue was dissolved in 10 ml of methanol, followed by cooled to 0° C. under stirring. Sodium borohydride was added 5 times at intervals of 5 hours, 1 g for each time, followed by further stirring at 0° C. overnight. Then the solvent was evaporated and a saturated aqueous solution of ammonium chloride was added to the residue, followed by extracting with ethyl acetate. The organic layer was washed with brine and dried over anhydrous magnesium sulfate. The solvent was evaporated, and the residue was purified by silica gel chromatography (hexane/ethyl acetate system), to give 107 mg of 3-bromo-5-(1-methyl-1,2,3,6-tetrahydropyridin-2-yl)-1-phenyl-1,2-dihydropyridin-2-one. The product was dissolved in 10 ml of dimethylformamide. 81 mg of 2-(2-cyanophenyl)-1,3,2-dioxaborinate, 142 mg of cesium carbonate and 7 mg of tetrakistriphenylphosphine palladium were added thereto, followed by stirring at 140° C. for 2 hours. After cooling to room temperature, water was added thereto, followed by extracting with ethyl acetate. The organic layer was washed with brine and dried over anhydrous magnesium sulfate. The solvent was evaporated, and the residue was purified by silica gel chromatography (hexane/ethyl acetate system), to give 41 mg of the title compound. After cooling to room temperature the solvent was evaporated The residue was dissolved in 10 ml of methanol by cooled to 0° C. under stirring Sodium borohydride was added 5 times at intervals of 5 hours, 1 g for each time by further stirring at 0° C. overnight Then the solvent was evaporated a saturated aqueous solution of ammonium chloride was added to the residue by extracting with ethyl acetate The organic layer was washed with brine dried over anhydrous magnesium sulfate The solvent was evaporated the residue was purified by silica gel chromatography (hexane/ethyl acetate system)

Conditions: temp:100.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 99 mg of 3-bromo-5-(2-pyridyl)-1-phenyl-1,2-dihydropyridin-2-one was dissolved in 10 ml of acetonitrile. 2 ml of methyl benzenesulfonate was added thereto, followed by stirring at 100° C. for 2 nights. After cooling to room temperature, the solvent was evaporated. The residue was dissolved in 10 ml of methanol, followed by cooled to 0° C. under stirring. Sodium borohydride was added 5 times at intervals of 5 hours, 1 g for each time, followed by further stirring at 0° C. overnight. Then the solvent was evaporated and a saturated aqueous solution of ammonium chloride was added to the residue, followed by extracting with ethyl acetate. The organic layer was washed with brine and dried over anhydrous magnesium sulfate. The solvent was evaporated, and the residue was purified by silica gel chromatography (hexane/ethyl acetate system), to give 107 mg of 3-bromo-5-(1-methyl-1,2,3,6-tetrahydropyridin-2-yl)-1-phenyl-1,2-dihydropyridin-2-one. The product was dissolved in 10 ml of dimethylformamide. 81 mg of 2-(2-cyanophenyl)-1,3,2-dioxaborinate, 142 mg of cesium carbonate and 7 mg of tetrakistriphenylphosphine palladium were added thereto, followed by stirring at 140° C. for 2 hours. After cooling to room temperature, water was added thereto, followed by extracting with ethyl acetate. The organic layer was washed with brine and dried over anhydrous magnesium sulfate. The solvent was evaporated, and the residue was purified by silica gel chromatography (hexane/ethyl acetate system), to give 41 mg of the title compound. After cooling to room temperature the solvent was evaporated The residue was dissolved in 10 ml of methanol by cooled to 0° C. under stirring Sodium borohydride was added 5 times at intervals of 5 hours, 1 g for each time by further stirring at 0° C. overnight Then the solvent was evaporated a saturated aqueous solution of ammonium chloride was added to the residue by extracting with ethyl acetate The organic layer was washed with brine dried over anhydrous magnesium sulfate The solvent was evaporated the residue was purified by silica gel chromatography (hexane/ethyl acetate system)

Conditions: temp:100.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 99 mg of 3-bromo-5-(2-pyridyl)-1-phenyl-1,2-dihydropyridin-2-one was dissolved in 10 ml of acetonitrile. 2 ml of methyl benzenesulfonate was added thereto, followed by stirring at 100° C. for 2 nights. After cooling to room temperature, the solvent was evaporated. The residue was dissolved in 10 ml of methanol, followed by cooled to 0° C. under stirring. Sodium borohydride was added 5 times at intervals of 5 hours, 1 g for each time, followed by further stirring at 0° C. overnight. Then the solvent was evaporated and a saturated aqueous solution of ammonium chloride was added to the residue, followed by extracting with ethyl acetate. The organic layer was washed with brine and dried over anhydrous magnesium sulfate. The solvent was evaporated, and the residue was purified by silica gel chromatography (hexane/ethyl acetate system), to give 107 mg of 3-bromo-5-(1-methyl-1,2,3,6-tetrahydropyridin-2-yl)-1-phenyl-1,2-dihydropyridin-2-one. The product was dissolved in 10 ml of dimethylformamide. 81 mg of 2-(2-cyanophenyl)-1,3,2-dioxaborinate, 142 mg of cesium carbonate and 7 mg of tetrakistriphenylphosphine palladium were added thereto, followed by stirring at 140° C. for 2 hours. After cooling to room temperature, water was added thereto, followed by extracting with ethyl acetate. The organic layer was washed with brine and dried over anhydrous magnesium sulfate. The solvent was evaporated, and the residue was purified by silica gel chromatography (hexane/ethyl acetate system), to give 41 mg of the title compound. After cooling to room temperature the solvent was evaporated The residue was dissolved in 10 ml of methanol by cooled to 0° C. under stirring Sodium borohydride was added 5 times at intervals of 5 hours, 1 g for each time by further stirring at 0° C. overnight Then the solvent was evaporated a saturated aqueous solution of ammonium chloride was added to the residue by extracting with ethyl acetate The organic layer was washed with brine dried over anhydrous magnesium sulfate The solvent was evaporated the residue was purified by silica gel chromatography (hexane/ethyl acetate system)

Conditions: temp:-20.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a cold (−20° C.) solution of 1-(3-chloro-4-fluorobenzyl)piperidin-2-one (340 g, 1.41 mol) in anhydrous tetrahydrofuran (5 L) under an atmosphere of nitrogen, a solution of lithium bis(trimethylsilyl)amide (3.09 L, 3.09 mol; 1M in TIE) was added over a period of 40 minutes with the temperature of the reaction maintained at −20° C. After the addition was complete, the reaction mixture was stirred at −20° C. for one hour. Methyl benzene sulfonate (231 mL, 1.69 mol) was added to the reaction mixture over a period of 30 minutes. The reaction mixture was stirred at −20° C. for 30 minutes. The product mixture was diluted with ethyl acetate (4 L) and washed with water (four times; 2 L each time). The organic extract was concentrated under vacuum. The residue was dissolved in toluene (4 L), treated with solid sodium carbonate (500 g), and heated at 100° C. for one hour. The product mixture was diluted with ethyl acetate (4 L) and washed with water (4 times; 2 L each). The organic extract was concentrated under vacuum. The residue was subjected to column chromatography on silica gel eluting with a gradient of 0-60% EtOAc in heptane. Collection and concentration of appropriate fractions provide the title compound as oil. After the addition The reaction mixture was stirred at −20° C. for 30 minutes washed with water (four times; 2 L each time) The organic extract was concentrated under vacuum The residue was dissolved in toluene (4 L) treated with solid sodium carbonate (500 g) heated at 100° C. for one hour The product mixture was diluted with ethyl acetate (4 L) washed with water (4 times; 2 L each) The organic extract was concentrated under vacuum Collection and concentration of appropriate fractions

Conditions: temp:100.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 99 mg of 3-bromo-5-(2-pyridyl)-1-phenyl-1,2-dihydropyridin-2-one was dissolved in 10 ml of acetonitrile. 2 ml of methyl benzenesulfonate was added thereto, followed by stirring at 100° C. for 2 nights. After cooling to room temperature, the solvent was evaporated. The residue was dissolved in 10 ml of methanol, followed by cooled to 0° C. under stirring. Sodium borohydride was added 5 times at intervals of 5 hours, 1 g for each time, followed by further stirring at 0° C. overnight. Then the solvent was evaporated and a saturated aqueous solution of ammonium chloride was added to the residue, followed by extracting with ethyl acetate. The organic layer was washed with brine and dried over anhydrous magnesium sulfate. The solvent was evaporated, and the residue was purified by silica gel chromatography (hexane/ethyl acetate system), to give 107 mg of 3-bromo-5-(1-methyl-1,2,3,6-tetrahydropyridin-2-yl)-1-phenyl-1,2-dihydropyridin-2-one. The product was dissolved in 10 ml of dimethylformamide. 81 mg of 2-(2-cyanophenyl)-1,3,2-dioxaborinate, 142 mg of cesium carbonate and 7 mg of tetrakistriphenylphosphine palladium were added thereto, followed by stirring at 140° C. for 2 hours. After cooling to room temperature, water was added thereto, followed by extracting with ethyl acetate. The organic layer was washed with brine and dried over anhydrous magnesium sulfate. The solvent was evaporated, and the residue was purified by silica gel chromatography (hexane/ethyl acetate system), to give 41 mg of the title compound. After cooling to room temperature the solvent was evaporated The residue was dissolved in 10 ml of methanol by cooled to 0° C. under stirring Sodium borohydride was added 5 times at intervals of 5 hours, 1 g for each time by further stirring at 0° C. overnight Then the solvent was evaporated a saturated aqueous solution of ammonium chloride was added to the residue by extracting with ethyl acetate The organic layer was washed with brine dried over anhydrous magnesium sulfate The solvent was evaporated the residue was purified by silica gel chromatography (hexane/ethyl acetate system)

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