5-甲基哌嗪-2-酮

反应条件: temp:120.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: ((2R)-4-(2-thiophenylsulfonyl)-1-(4-(2,2,2-trifluoro-1-hydroxy-1-methylethyl)phenyl)-2-piperazinyl)methyl methanesulfonate (350 mg, 0.662 mmol, Intermediate B) was combined with 5-methylpiperazin-2-one (79 mg, 0.695 mmol, Anichem, North Brunswick, N.J.), potassium carbonate (275 mg, 1.99 mmol, Sigma-Aldrich, St. Louis, Mo.) in acetonitrile (4.41 mL) was heated at 120° C. for 30 min. After the reaction was allowed to cool to room temperature, the mixture was diluted with EtOAc and the solids were removed by filtering through a 0.2 μm millipore Millex-FG filter (Millipore, Billerica, Mass.). The filtrate was concentrated and purified by reverse-phase HPLC (Phenomenex Gemini-NX 10μ, 110 Å, AXIA packed column, 100×50 mm, 60 mL/min, 10-95% CH3CN/H2O, 0.1% TFA, 10 min gradient). The collected fractions were partitioned between CH2Cl2 and saturated aqueous NaHCO3, the organic layer was dried (Na2SO4), filtered and concentrated. The residue was taken up in MeOH and was passed through an AccuBond SPE SCX cartridge eluting with 2M ammonia/MeOH, to give the title compound (28 mg) as a mixture of four diastereomers. to cool to room temperature the solids were removed by filtering through a 0.2 μm millipore Millex-FG filter (Millipore, Billerica, Mass.) The filtrate was concentrated purified by reverse-phase HPLC (Phenomenex Gemini-NX 10μ, 110 Å, AXIA packed column, 100×50 mm, 60 mL/min, 10-95% CH3CN/H2O, 0.1% TFA, 10 min gradient) The collected fractions were partitioned between CH2Cl2 and saturated aqueous NaHCO3 the organic layer was dried (Na2SO4) filtered concentrated eluting with 2M ammonia/MeOH