4-benzylpiperazin-1-amine

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:

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

実験手順: 2-(1,3-Dioxo-1,3-dihydro-isoindol-2-yl)-ethanesulfonic acid (4-benzyl-piperazin-1-yl)-amide was prepared by an analogous procedure as described for example 1 i) starting from 140 mg (0.73 mmol) 4-benzyl-piperazin-1-ylamine and 200 mg (1 equiv.) 2-(1,3-dioxo-1,3-dihydro-isoindol-2-yl)-ethanesulfonyl chloride. The product was obtained in crude form as a light yellow foam. The product was obtained in crude form as a light yellow foam

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

実験手順: A mixture of 4-bromobenzotrifluoride (3.00 g, 13.3 mmol), 4-benzylpiperazin-1-yl-amine (3.06 g, 16.0 mmol), palladium acetate (60 mg, 0.267 mmol), (S)-(−)-BINAP (174 mg, 0.280 mmol) and sodium tert-butoxide (1.92 g, 20.0 mmol) in toluene (60 ml) was refluxed under a nitrogen atmosphere for 7 hours. Water was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The extract was washed with brine, dried over sodium sulfate, and then filtered. The filtrate was concentrated under reduced pressure, and the residue was then purified by silica gel column chromatography (n-hexane/acetone=4/1) to afford (4-benzylpiperazin-1-yl)-(4-trifluoromethylphenyl)amine (2.666 g, yield 59%) as a pale yellow oil. was refluxed under a nitrogen atmosphere for 7 hours the mixture was extracted with ethyl acetate The extract was washed with brine dried over sodium sulfate filtered The filtrate was concentrated under reduced pressure the residue was then purified by silica gel column chromatography (n-hexane/acetone=4/1)

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

実験手順: A mixture of 4-bromobenzotrifluoride (3.00 g, 13.3 mmol), 4-benzylpiperazin-1-yl-amine (3.06 g, 16.0 mmol), palladium acetate (60 mg, 0.267 mmol), (S)-(−)-BINAP (174 mg, 0.280 mmol) and sodium tert-butoxide (1.92 g, 20.0 mmol) in toluene (60 ml) was refluxed under a nitrogen atmosphere for 7 hours. Water was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The extract was washed with brine, dried over sodium sulfate, and then filtered. The filtrate was concentrated under reduced pressure, and the residue was then purified by silica gel column chromatography (n-hexane/acetone=4/1) to afford (4-benzylpiperazin-1-yl)-(4-trifluoromethylphenyl)amine (2.666 g, yield 59%) as a pale yellow oil. was refluxed under a nitrogen atmosphere for 7 hours the mixture was extracted with ethyl acetate The extract was washed with brine dried over sodium sulfate filtered The filtrate was concentrated under reduced pressure the residue was then purified by silica gel column chromatography (n-hexane/acetone=4/1)

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

実験手順: To a solution of 4-benzylpiperazin-1-yl-amine (43.18 g, 225 mmol) in etanol (400 ml), a suspension of 20% palladium hydroxide/carbon (6.50 g) in etanol (30 ml) was added, and the mixture was stirred at room temperature under an atmospheric pressure of hydrogen for 3 hours and then at 50° C. for 2 hours. The reaction mixture was filtered through Celite, 4-(trifluoromethoxy)benzaldehyde (42.92 g, 225 mmol) was added to the filtrate, and the mixture was stirred at room temperature for 1.5 hours. The reaction mixture was concentrated under reduced pressure, and the residue was purified by silica gel column chromatography (methylene chloride/methanol=10/1) to afford piperazin-1-yl-(4-trifluoromethoxybenzylidene)amine (56.88 g, yield 93%) as a pale yellow crystalline powder. was added was added to the filtrate The reaction mixture was concentrated under reduced pressure the residue was purified by silica gel column chromatography (methylene chloride/methanol=10/1)

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

実験手順: 2-(1,3-Dioxo-1,3-dihydro-isoindol-2-yl)-ethanesulfonic acid (4-benzyl-piperazin-1-yl)-amide was prepared by an analogous procedure as described for example 1 i) starting from 140 mg (0.73 mmol) 4-benzyl-piperazin-1-ylamine and 200 mg (1 equiv.) 2-(1,3-dioxo-1,3-dihydro-isoindol-2-yl)-ethanesulfonyl chloride. The product was obtained in crude form as a light yellow foam. The product was obtained in crude form as a light yellow foam

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

実験手順: A solution of tert-butyl (3-oxopropyl)carbamate (4.2 g) and 4-benzylpiperazin-1-amine (4.6 g) in methanol (60 mL) was heated under reflux for 3 hours, and the solvent was distilled off under reduced pressure. After the residue was dissolved in methanol (60 mL), acetic acid (4.1 mL) and sodium triacetoxyborohydride (3.2 g) were added thereto, and the mixture was stirred at room temperature for 15 hours. The reaction mixture was concentrated under reduced pressure, made alkaline with 1N sodium hydroxide and potassium carbonate, and extracted with dichloromethane. The organic layer was dried over anhydrous sodium sulfate, and the solvent was distilled off under reduced pressure. The residue obtained was dissolved in ethyl acetate (10 mL). and then a 4N hydrochloric acid-ethyl acetate solution (100 ml) was slowly added at 0° C., followed by stirring at room temperature for 5 hours. The precipitate was collected by filtration, dried, and then suspended in acetonitrile (200 mL). DBU (14.6 g) and CDI (7.8 g) were added thereto, and the mixture was heated under reflux for 15 hours. The reaction mixture was concentrated under reduced pressure, and the residue was diluted with an aqueous sodium bicarbonate solution and extracted with dichloromethane. The extract was dried over anhydrous sodium sulfate, and the solvent was distilled off under reduced pressure. The residue was purified by basic silica gel column chromatography (ethyl acetate), and recrystallized from diethyl ether to obtain the title compound (3.1 g, 46%) as white crystals. under reflux for 3 hours the solvent was distilled off under reduced pressure After the residue was dissolved in methanol (60 mL) acetic acid (4.1 mL) and sodium triacetoxyborohydride (3.2 g) were added The reaction mixture was concentrated under reduced pressure extracted with dichloromethane The organic layer was dried over anhydrous sodium sulfate the solvent was distilled off under reduced pressure The residue obtained by stirring at room temperature for 5 hours The precipitate was collected by filtration dried DBU (14.6 g) and CDI (7.8 g) were added the mixture was heated under reflux for 15 hours The reaction mixture was concentrated under reduced pressure the residue was diluted with an aqueous sodium bicarbonate solution extracted with dichloromethane The extract was dried over anhydrous sodium sulfate the solvent was distilled off under reduced pressure The residue was purified by basic silica gel column chromatography (ethyl acetate) recrystallized from diethyl ether

反応条件: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A mixture of 3-methyldihydrofuran-2(3H)-one (2.0 g), thionyl chloride (1.5 ml) and zinc chloride (10 mg) was stirred at 80° C. for 15 hours. The mixture was cooled to room temperature, and the reaction mixture was added dropwise to a solution of 4-benzylpiperazin-1-amine (3.8 g) in THF (50 mL) at 0° C., followed by stirring at 0° C. for 2 hours. Sodium hydride (60% in oil; 2.4 g) was added thereto and the mixture was stirred at room temperature for 15 hours. Ice was added thereto, and then the reaction mixture was concentrated under reduced pressure. The residue was diluted with water, and extracted with dichloromethane. The extract was dried over anhydrous sodium sulfate, and the solvent was distilled off under reduced pressure. The residue obtained was purified by basic silica gel column chromatography (ethyl acetate/hexane=1/5) to obtain the title compound (2.0 g, 37%) as a yellow oil. The mixture was cooled to room temperature by stirring at 0° C. for 2 hours the mixture was stirred at room temperature for 15 hours Ice was added the reaction mixture was concentrated under reduced pressure The residue was diluted with water extracted with dichloromethane The extract was dried over anhydrous sodium sulfate the solvent was distilled off under reduced pressure The residue obtained was purified by basic silica gel column chromatography (ethyl acetate/hexane=1/5)

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir: