1-(3-chlorophenyl)piperazin-2-one;hydrochloride

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

実験手順: The carboxylic acid from Step D (5.14 g, 16.1 mmol), 1-(3-chlorophenyl)piperazin-2-one hydrochloride (3.97 g, 16.1 mmol) (prepared as described in U.S. Pat. No. 5,856,326), EDC hydrochloride (3.70 g, 19.3 mmol), HOBT (2.61 g, 19.3 mmol), and N,N-diisopropylethylamine (14.0 mL, 80.4 mmol) were stirred in dry, degassed DMF (50 mL) at 25° C. for 16 hours. The reaction was poured onto saturated aqueous sodium bicarbonate solution and extracted with methylene chloride (3×100 mL). The combined organic layers were washed with brine, dried over sodium sulfate, filtered, and concentrated in vacuo to provide a yellow oil. The crude product was purified by column chromatography (3→5% methanol/methylene chloride) and converted to the HCl salt to provide the title compound as a yellow solid. in dry degassed DMF (50 mL) at 25° C. for 16 hours The reaction was poured onto saturated aqueous sodium bicarbonate solution extracted with methylene chloride (3×100 mL) The combined organic layers were washed with brine dried over sodium sulfate filtered concentrated in vacuo to provide a yellow oil The crude product was purified by column chromatography (3→5% methanol/methylene chloride)

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

実験手順: The carboxylic acid from Step D (5.14 g, 16.1 mmol), 1-(3-chlorophenyl)piperazin-2-one hydrochloride (3.97 g, 16.1 mmol) (prepared as described in U.S. Pat. No. 5,856,326), EDC hydrochloride (3.70 g, 19.3 mmol), HOBT (2.61 g, 19.3 mmol), and N,N-diisopropylethylamine (14.0 mL, 80.4 mmol) were stirred in dry, degassed DMF (50 mL) at 25° C. for 16 hours. The reaction was poured onto saturated aqueous sodium bicarbonate solution and extracted with methylene chloride (3×100 mL). The combined organic layers were washed with brine, dried over sodium sulfate, filtered, and concentrated in vacuo to provide a yellow oil. The crude product was purified by column chromatography (3→5% methanol/methylene chloride) and converted to the HCl salt to provide the title compound as a yellow solid. in dry degassed DMF (50 mL) at 25° C. for 16 hours The reaction was poured onto saturated aqueous sodium bicarbonate solution extracted with methylene chloride (3×100 mL) The combined organic layers were washed with brine dried over sodium sulfate filtered concentrated in vacuo to provide a yellow oil The crude product was purified by column chromatography (3→5% methanol/methylene chloride)

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

実験手順: The carboxylic acid from Step D (5.14 g, 16.1 mmol), 1-(3-chlorophenyl)piperazin-2-one hydrochloride (3.97 g, 16.1 mmol) (prepared as described in U.S. Pat. No. 5,856,326), EDC hydrochloride (3.70 g, 19.3 mmol), HOBT (2.61 g, 19.3 mmol), and N,N-diisopropylethylamine (14.0 mL, 80.4 mmol) were stirred in dry, degassed DMF (50 mL) at 25° C. for 16 hours. The reaction was poured onto saturated aqueous sodium bicarbonate solution and extracted with methylene chloride (3×100 mL). The combined organic layers were washed with brine, dried over sodium sulfate, filtered, and concentrated in vacuo to provide a yellow oil. The crude product was purified by column chromatography (3→5% methanol/methylene chloride) and converted to the HCl salt to provide the title compound as a yellow solid. in dry degassed DMF (50 mL) at 25° C. for 16 hours The reaction was poured onto saturated aqueous sodium bicarbonate solution extracted with methylene chloride (3×100 mL) The combined organic layers were washed with brine dried over sodium sulfate filtered concentrated in vacuo to provide a yellow oil The crude product was purified by column chromatography (3→5% methanol/methylene chloride)