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

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Through a solution of Boc-protected piperazinone from Step D (17.19 g, 55.4 mmol) in 500 mL of EtOAc at -78° C. was bubbled anhydrous HCl gas. The saturated solution was warmed to 0° C., and stirred for 12 hours. Nitrogen gas was bubbled through the reaction to remove excess HCl, and the mixture was warmed to room temperature. The solution was concentrated in vacuo to provide the hydrochloride as a white powder. This material was taken up in 300 mL of CH2Cl2 and treated with dilute aqueous NaHCO3 solution. The aqueous phase was extracted with CH2Cl2 (8×300 mL) until the analysis indicated complete extraction. The combined organic mixture was dried (Na2SO4), filtered, and concentrated in vacuo to provide the titled free amine as a pale brown oil. Nitrogen gas was bubbled through the reaction to remove excess HCl the mixture was warmed to room temperature The solution was concentrated in vacuo

反応条件: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Through a solution of Boc-protected piperazinone from Step D (17.19 g, 55.4 mmol) in 500 mL of EtOAc at -78° C. was bubbled anhydrous HCl gas. The saturated solution was warmed to 0° C., and stirred for 12 hours. Nitrogen gas was bubbled through the reaction to remove excess HCl, and the mixture was warmed to room temperature. The solution was concentrated in vacuo to provide the hydrochloride as a white powder. This material was taken up in 300 mL of CH2Cl2 and treated with dilute aqueous NaHCO3 solution. The aqueous phase was extracted with CH2Cl2 (8×300 mL) until the analysis indicated complete extraction. The combined organic mixture was dried (Na2SO4), filtered, and concentrated in vacuo to provide the titled free amine as a pale brown oil. Nitrogen gas was bubbled through the reaction to remove excess HCl the mixture was warmed to room temperature The solution was concentrated in vacuo

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: The titled compound was prepared from the product of Step F (264 mg, 0.89 mmol) and the product of Step J of Example 1 using the procedure described in Step K of Example 1. Purification by silica gel column chromatography (50-65% acetoneldichloro methane) and conversion to the dihydrochloride salt using excess ethereal HCl solution gave the titled product as a white powder. Purification by silica gel column chromatography (50-65% acetoneldichloro methane) and conversion to the dihydrochloride salt

反応条件: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Through a solution of Boc-protected piperazinone from Step I (17.19 g, 55.4 mmol) in 500 mL of EtOAc at −78° C. was bubbled anhydrous HCl gas. The saturated solution was warmed to 0° C., and stirred for 12 hours. Nitrogen gas was bubbled through the reaction to remove excess HCl, and the mixture was warmed to room temperature. The solution was concentrated in vacuo to provide the hydrochloride as a white powder. This material was taken up in 300 mL of CH2Cl2 and treated with dilute aqueous NaHCO3 solution. The aqueous phase was extracted with CH2Cl2 (8×300 mL) until the analysis indicated complete extraction. The combined organic mixture was dried (Na2SO4), filtered, and concentrated in vacuo to provide the titled free amine as a pale brown oil. Nitrogen gas was bubbled through the reaction to remove excess HCl the mixture was warmed to room temperature The solution was concentrated in vacuo

反応条件: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Through a solution of Boc-protected piperazinone from Step I (17.19 g, 55.4 mmol) in 500 mL of EtOAc at -78° C. was bubbled anhydrous HCl gas. The saturated solution was warmed to 0° C., and stirred for 12 hours. Nitrogen gas was bubbled through the reaction to remove excess HCl, and the mixture was warmed to room temperature. The solution was concentrated in vacuo to provide the hydrochloride as a white powder. This material was taken up in 300 mL of CH2Cl2 and treated with dilute aqueous NaHCO3 solution. The aqueous phase was extracted with CH2Cl2 (8×300 mL) until tlc analysis indicated complete extraction. The combined organic mixture was dried (Na2SO4), filtered, and concentrated in vacuo to provide the titled free amine as a pale brown oil. Nitrogen gas was bubbled through the reaction to remove excess HCl the mixture was warmed to room temperature The solution was concentrated in vacuo

反応条件: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Through a solution of Boc-protected piperazinone from Step D (17.19 g, 55.4 mmol) in 500 mL of EtOAc at −78° C. was bubbled anhydrous HC1 gas. The saturated solution was warmed to 0° C., and stirred for 12 hours. Nitrogen gas was bubbled through the reaction to remove excess HC1, and the mixture was warmed to room temperature. The solution was concentrated in vacuo to provide the hydrochloride as a white powder. This material was taken up in 300 mL of CH2Cl2 and treated with dilute aqueous NaHCO3 solution. The aqueous phase was extracted with CH2Cl2 (8×300 mL) until tlc analysis indicated complete extraction. The combined organic mixture was dried (Na2SO4), filtered, and concentrated in vacuo to provide the titled free amine as a pale brown oil. Nitrogen gas was bubbled through the reaction to remove excess HC1 the mixture was warmed to room temperature The solution was concentrated in vacuo

反応条件: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Through a solution of Boc-protected piperazinone from Step D (17.19 g, 55.4 mmol) in 500 mL of EtOAc at -78° C. was bubbled anhydrous HCl gas. The saturated solution was warmed to 0° C., and stirred for 12 hours. Nitrogen gas was bubbled through the reaction to remove excess HCl, and the mixture was warmed to room temperature. The solution was concentrated in vacuo to provide the hydrochloride as a white powder. This material was taken up in 300 mL of CH2Cl2 and treated with dilute aqueous NaHCO3 solution. The aqueous phase was extracted with CH2Cl2 (8×300 mL) until the analysis indicated complete extraction. The combined organic mixture was dried (Na2SO4), filtered, and concentrated in vacuo to provide the titled free amine as a pale brown oil. Nitrogen gas was bubbled through the reaction to remove excess HCl the mixture was warmed to room temperature The solution was concentrated in vacuo