Cl[CH2:2][C:3]([N:5]1[CH2:10][CH2:9][N:8]([C:11]2[CH:16]=[CH:15][C:14]([Cl:17])=[C:13]([O:18][CH3:19])[CH:12]=2)[CH2:7][CH2:6]1)=[O:4].[F:20][C:21]1[CH:30]=[CH:29][C:24]2[NH:25][C:26](=[O:28])[O:27][C:23]=2[CH:22]=1.C([O-])([O-])=O.[K+].[K+]>CN1C(=O)CCC1>[F:20][C:21]1[CH:30]=[CH:29][C:24]2[N:25]([CH2:2][C:3]([N:5]3[CH2:10][CH2:9][N:8]([C:11]4[CH:16]=[CH:15][C:14]([Cl:17])=[C:13]([O:18][CH3:19])[CH:12]=4)[CH2:7][CH2:6]3)=[O:4])[C:26](=[O:28])[O:27][C:23]=2[CH:22]=1In a 4 mL vial was added 2-chloro-1-[4-(4-chloro-3-methoxy-phenyl)-piperazin-1-yl]-ethanone (1) (59 mg, 0.20 mmol, 1.0 equiv), 6-fluoro-3H-benzooxazol-2-one (30 mg, 0.20 mmol, 1.00 equiv), K2CO3 (110 mg, 0.80 mmol, 4.0 equiv) and 800 μL of NMP. A stir bar was placed in the vial and the vial was then capped. The resultant mixture stirred at 60° C. overnight. The crude product was purified by reversed phase HPLC (acetonitrile —H2O with 0.1% TFA as the eluent) to yield 6-fluoro-3-{2-[4-(4-chloro-3-methoxy-phenyl)-piperazin-1-yl]-2-oxo-ethyl}-3H-benzooxazol-2-one (18): HPLC retention time, 2.35 minutes (Agilent Zorbax SB-C18, 2.1×50 mm, 5μ, 35° C.) using 1 ml/min flow rate, a 2.5 minute gradient of 20% to 100% B with a 1.1 minute wash at 100% B (A=0.1% formic acid/5% acetonitrile/94.9% water, B=0.1% formic acid/5% water/94.9% acetonitrile); MS (ES) M+H expected, 419.8, found, 419.9.
Loading…