4-(chloromethyl)-N-phenylbenzamide

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

実験手順: An acetonitrile (100 mL) solution of 4-(N-phenylcarbamoyl)benzyl chloride (800 mg, 3.26 mmol) was dropped into a mixture of 4-[[N-(9-fluorenylmethyloxycarbonyl)glycyl]aminomethyl]piperidine (1.27 g, 2.96 mmol) with triethylamine (1.25 mL, 8.88 mmol), KI (50 mg, 0.30 mmol) and acetonitrile (200 mL). The resulting mixture was stirred at room temperature for 19 hours and stirred at 60° C. for another 5 hours. After concentrating, the obtained crude product was purified by column chromatography (SiO2, 5% methanol/dichloromethane-triethylamine/methanol/dichloromethane=2:2:96) to provide 4-[(glycylamino)methyl]-1-[4-(N-phenylcarbamoyl)benzyl]piperidine (340 mg, 30%). stirred at 60° C. for another 5 hours After concentrating the obtained crude product was purified by column chromatography (SiO2, 5% methanol/dichloromethane-triethylamine/methanol/dichloromethane=2:2:96)

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

実験手順: An acetonitrile (100 mL) solution of 4-(N-phenylcarbamoyl)benzyl chloride (800 mg, 3.26 mmol) was dropped into a mixture of 4-[[N-(9-fluorenylmethyloxycarbonyl)glycyl]aminomethyl]piperidine (1.27 g, 2.96 mmol) with triethylamine (1.25 mL, 8.88 mmol), KI (50 mg, 0.30 mmol) and acetonitrile (200 mL). The resulting mixture was stirred at room temperature for 19 hours and stirred at 60° C. for another 5 hours. After concentrating, the obtained crude product was purified by column chromatography (SiO2, 5% methanol/dichloromethane-triethylamine/methanol/dichloromethane=2:2:96) to provide 4-[(glycylamino)methyl]-1-[4-(N-phenylcarbamoyl)benzyl]piperidine (340 mg, 30%). stirred at 60° C. for another 5 hours After concentrating the obtained crude product was purified by column chromatography (SiO2, 5% methanol/dichloromethane-triethylamine/methanol/dichloromethane=2:2:96)

反応条件: temp:60.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a mixture of 4-[{N-(9-fluorenylmethyloxycarbonyl)glycyl}aminomethyl]piperidine (1.27 g, 2.96 mmol), Et3N (1.25 mL, 8.88 mmol), KI (50 mg, 0.30 mmol) and CH3CN (200 mL) was added dropwise a solution of 4-(N-phenylcarbamoyl)benzyl chloride (800 mg, 3.26 mmol) in CH3 CN (100 mL). The mixture was stirred at room temperature for 19 h and at 60° C. for 5 h. Concentration and column chromatography (SiO2, 5% CH3OH/CH2Cl2-Et3N:CH3OH:CH2Cl2=2:2:96) afforded 4-{(glycylamino)methyl}-1-{4-(N-phenylcarbamoyl)benzyl}piperidine (340 mg, 30%). Concentration and column chromatography (SiO2, 5% CH3OH/CH2Cl2-Et3N:CH3OH:CH2Cl2=2:2:96)

反応条件: temp:10.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: In a 200 ml four-necked flask equipped with a stirrer and a thermometer, 1.34 g (10.6 mmol) of 4-mercaptophenol, 0.7 g (10.6 mmol) of potassium hydroxide and 50 ml of methanol were added at room temperature. After confirming that potassium hydroxide has been dissolved, the inner temperature was cooled to 10° C. and 2.6 g (10.6 mmol) of 4-chloromethyl-N-phenylbenzamide was added, followed by stirring at room temperature for 3 hours. After the completion of the reaction, the reaction solution was acidified with hydrochloric acid and 50 ml of water was added, and then the deposited crystal was collected by filtration to obtain 3.0 g of 4-(4-hydroxyphenylthiomethyl)-N-phenylbenzamide. The yield was 84%. The melting point was 220–222° C. In a 200 ml four-necked flask equipped with a stirrer has been dissolved After the completion of the reaction was added the deposited crystal was collected by filtration

反応条件: temp:60.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a mixture of 4-[{N-(9-fluorenylmethyloxycarbonyl)glycyl}aminomethyl]piperidine (1.27 g, 2.96 mmol), Et3N (1.25 mL, 8.88 mmol), KI (50 mg, 0.30 mmol) and CH3CN (200 mL) was added dropwise a solution of 4-(N-phenylcarbamoyl)benzyl chloride (800 mg, 3.26 mmol) in CH3CN (100 mL). The mixture was stirred at room temperature for 19 h and at 60° C. for 5 h. Concentration and column chromatography (SiO2, 5% CH3OH/CH2Cl2-Et3N:CH3OH:CH2C2=2:2:96) afforded 4-{(glycylamino)methyl}-1-{4-(N-phenylcarbamoyl)benzyl}piperidine (340 mg, 30%). Concentration and column chromatography (SiO2, 5% CH3OH/CH2Cl2-Et3N:CH3OH:CH2C2=2:2:96)

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

実験手順: An acetonitrile (100 mL) solution of 4-(N-phenylcarbamoyl)benzyl chloride (800 mg, 3.26 mmol) was dropped into a mixture of 4-[[N-(9-fluorenylmethyloxycarbonyl)glycyl]aminomethyl]piperidine (1.27 g, 2.96 mmol) with triethylamine (1.25 mL, 8.88 mmol), KI (50 mg, 0.30 mmol) and acetonitrile (200 mL). The resulting mixture was stirred at room temperature for 19 hours and stirred at 60° C. for another 5 hours. After concentrating, the obtained crude product was purified by column chromatography (SiO2, 5% methanol/dichloromethane-triethylamine/methanol/dichloromethane=2:2:96) to provide 4-[(glycylamino)methyl]-1-[4-(N-phenylcarbamoyl)benzyl]piperidine (340 mg, 30%). stirred at 60° C. for another 5 hours After concentrating the obtained crude product was purified by column chromatography (SiO2, 5% methanol/dichloromethane-triethylamine/methanol/dichloromethane=2:2:96)