tert-butyl 4-[[(2-aminoacetyl)amino]methyl]piperidine-1-carboxylate

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: A solution of 4-{(glycylamino)methyl}-1-(tert-butoxycarbonyl)piperidine (1.33 g, 4.90 mmol) in CH2Cl2 (25 mL) was treated with EtN (0.75 mL, 5.4 mmol), 2-amino-5-chlorobenzoic acid (840 mg, 4.9 mmol), EDCI (940 mg, 4.9 mmol) and HOBt (660 mg, 4.9 mmol). After the reaction mixture was stirred at room temperature for 3 h, 2 N aqueous NaOH solution (20 mL) was added. The organic layer was separated, and the aqueous layer was extracted with dichloromethane (20 mL×3). The combined organic layers were dried over anhydrous sodium sulfate, filtered, and concentrated. Column chromatography (SiO2, ethyl acetate) afforded the desired 4-[{(N-(2-amino-5-chlorobenzoyl)glycyl)amino}methyl]-1-(tert-butoxycarbonyl)piperidine (1.63 g, 78%) as a solid. The organic layer was separated the aqueous layer was extracted with dichloromethane (20 mL×3) The combined organic layers were dried over anhydrous sodium sulfate filtered concentrated

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

実験手順: A solution of 4-{(glycylamino)methyl}-1-(tert-butoxycarbonyl)piperidine (1.33 g, 4.90 mmol) in CH2Cl2 (25 mL) was treated with EtN (0.75 mL, 5.4 mmol), 2-amino-5-chlorobenzoic acid (840 mg, 4.9 mmol), EDCI (940 mg, 4.9 mmol) and HOBt (660 mg, 4.9 mmol). After the reaction mixture was stirred at room temperature for 3 h, 2 N aqueous NaOH solution (20 mL) was added. The organic layer was separated, and the aqueous layer was extracted with dichloromethane (20 mL×3). The combined organic layers were dried over anhydrous sodium sulfate, filtered, and concentrated. Column chromatography (SiO2, ethyl acetate) afforded the desired 4-[{(N-(2-amino-5-chlorobenzoyl)glycyl)amino}methyl]-1-(tert-butoxycarbonyl)piperidine (1.63 g, 78%) as a solid. The organic layer was separated the aqueous layer was extracted with dichloromethane (20 mL×3) The combined organic layers were dried over anhydrous sodium sulfate filtered concentrated

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

実験手順: A solution of 4-[{(N-(benzyloxycarbonyl)glycyl)amino}methyl]-1-(tert-butoxycarbonyl)piperidine (6.26 g, 15.4 mmol) in methanol (100 mL) was hydrogenated at 1 atm in the presence of 5% palladium on charcoal (620 mg) at room temperature for 7 h. The catalyst was removed by filtration through Celite and the combined filtrate was concentrated to afford 4-{(glycylamino)methyl}-1-(tert-butoxycarbonyl)piperidine (3.84 g, 92%) as a solid. The catalyst was removed by filtration through Celite the combined filtrate was concentrated

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

実験手順: A solution of 4-[{(N-(benzyloxycarbonyl)glycyl)amino}methyl]-1-(tert-butoxycarbonyl)piperidine (6.26 g, 15.4 mmol) in methanol (100 mL) was hydrogenated at 1 atm in the presence of 5% palladium on charcoal (620 mg) at room temperature for 7 h. The catalyst was removed by filtration through Celite and the combined filtrate was concentrated to afford 4-{(glycylamino)methyl}-1-(tert-butoxycarbonyl)piperidine (3.84 g, 92%) as a solid. The catalyst was removed by filtration through Celite the combined filtrate was concentrated

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

実験手順: A solution of 4-{(glycylamino)methyl}-1-(tert-butoxycarbonyl)piperidine (1.33 g, 4.90 mmol) in CH2Cl2 (25 mL) was treated with EtN (0.75 mL, 5.4 mmol), 2-amino-5-chlorobenzoic acid (840 mg, 4.9 mmol), EDCI (940 mg, 4.9 mmol) and HOBt (660 mg, 4.9 mmol). After the reaction mixture was stirred at room temperature for 3 h, 2 N aqueous NaOH solution (20 mL) was added. The organic layer was separated, and the aqueous layer was extracted with dichloromethane (20 mL×3). The combined organic layers were dried over anhydrous sodium sulfate, filtered, and concentrated. Column chromatography (SiO2, ethyl acetate) afforded the desired 4-[{(N-(2-amino-5-chlorobenzoyl)glycyl)amino}methyl]-1-(tert-butoxycarbonyl)piperidine (1.63 g, 78%) as a solid. The organic layer was separated the aqueous layer was extracted with dichloromethane (20 mL×3) The combined organic layers were dried over anhydrous sodium sulfate filtered concentrated

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

実験手順: A solution of 4-[{(N-(benzyloxycarbonyl)glycyl)amino}methyl]-1-(tert-butoxycarbonyl)piperidine (6.26 g, 15.4 mmol) in methanol (100 mL) was hydrogenated at 1 atm in the presence of 5% palladium on charcoal (620 mg) at room temperature for 7 h. The catalyst was removed by filtration through Celite and the combined filtrate was concentrated to afford 4-{(glycylamino)methyl}-1-(tert-butoxycarbonyl)piperidine (3.84 g, 92%) as a solid. The catalyst was removed by filtration through Celite the combined filtrate was concentrated

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

実験手順: Triethylamine (0.75 mL, 5.4 mmol), 2-amino-5-chlorobenzoic acid (840 mg, 4.9 mmol), EDCI (940 mg, 4.9 mmol) and HOBt (660 mg, 4.9 mmol) were added to a chloroform (25 mL) solution of 4-[(glycylamino)methyl]-1-(tert-butoxycarbonyl)piperidine (1.33 g, 4.90 mmol). The resulting mixture was stirred at room temperature for 3 hours, and a 2 M aqueous solution of NaOH (20 mL) was then added to the mixture. The organic layer was separated, and the aqueous layer was extracted with dichloromethane (20 mL×3). The organic layers were combined, dried over anhydrous sodium sulfate, filtered and concentrated. The obtained crude product was purified by column chromatography (SiO2, ethyl acetate) to thereby provide 4-[[(N-(2-amino-5-chlorobenzoyl) glycyl)amino]methyl]-1-(tert-butoxycarbonyl)piperidine as a solid (1.63 g, 78%). The organic layer was separated the aqueous layer was extracted with dichloromethane (20 mL×3) dried over anhydrous sodium sulfate filtered concentrated The obtained crude product was purified by column chromatography (SiO2, ethyl acetate) to thereby provide 4-[[(N-(2-amino-5-chlorobenzoyl) glycyl)amino]methyl]-1-(tert-butoxycarbonyl)piperidine as a solid (1.63 g, 78%)

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

実験手順: A methanol (100 mL) solution of 4-[[(N-(benzyloxycarbonyl)glycyl)amino]methyl]-1-(tert-butoxycarbonyl)piperidine (6.26 g, 15.4 mmol) was hydrogenated in the presence of a 5% palladium carbon (620 mg) at room temperature for 7 hours. The catalyst was removed by filtration through Celite, and the filtrate was then concentrated to thereby afford 4-[(glycylamino)methyl]-1-(tert- butoxycarbonyl)piperidine as a solid (3.84 g, 92%). The catalyst was removed by filtration through Celite the filtrate was then concentrated to thereby afford 4-[(glycylamino)methyl]-1-(tert- butoxycarbonyl)piperidine as a solid (3.84 g, 92%)

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: Triethylamine (0.75 mL, 5.4 mmol), 2-amino-5-chlorobenzoic acid (840 mg, 4.9 mmol), EDCI (940 mg, 4.9 mmol) and HOBt (660 mg, 4.9 mmol) were added to a chloroform (25 mL) solution of 4-[(glycylamino)methyl]-1-(tert-butoxycarbonyl)piperidine (1.33 g, 4.90 mmol). The resulting mixture was stirred at room temperature for 3 hours, and a 2 M aqueous solution of NaOH (20 mL) was then added to the mixture. The organic layer was separated, and the aqueous layer was extracted with dichloromethane (20 mL×3). The organic layers were combined, dried over anhydrous sodium sulfate, filtered and concentrated. The obtained crude product was purified by column chromatography (SiO2, ethyl acetate) to thereby provide 4-[[(N-(2-amino-5-chlorobenzoyl) glycyl)amino]methyl]-1-(tert-butoxycarbonyl)piperidine as a solid (1.63 g, 78%). The organic layer was separated the aqueous layer was extracted with dichloromethane (20 mL×3) dried over anhydrous sodium sulfate filtered concentrated The obtained crude product was purified by column chromatography (SiO2, ethyl acetate) to thereby provide 4-[[(N-(2-amino-5-chlorobenzoyl) glycyl)amino]methyl]-1-(tert-butoxycarbonyl)piperidine as a solid (1.63 g, 78%)