[O:1]=[C:2]1[NH:7][CH2:6][CH2:5][N:4]([C:8]([O:10][C:11]([CH3:14])([CH3:13])[CH3:12])=[O:9])[CH2:3]1.Br[C:16]1[CH:21]=[CH:20][C:19]([F:22])=[CH:18][CH:17]=1.CN(C)CCN>C1(C)C=CC=CC=1.C(OCC)(=O)C.[Cu]I>[F:22][C:19]1[CH:20]=[CH:21][C:16]([N:7]2[CH2:6][CH2:5][N:4]([C:8]([O:10][C:11]([CH3:14])([CH3:13])[CH3:12])=[O:9])[CH2:3][C:2]2=[O:1])=[CH:17][CH:18]=1
To a solution of tert-butyl 3-oxopiperazine-1-carboxylate (prepared according to procedure reported in JP2005504737, 2.0 g, 9.99 mmol), 1-bromo-4-fluorobenzene (1.748 g, 9.99 mmol), N,N-dimethylethylenediamine (0.070 g, 0.799 mmol) and potassium hydrophosphate (KHPO4) (3.13 g, 17.98 mmol) in toluene (10 ml) was added copper (I)iodide (0.101 g, 0.529 mmol) at 25° C. The reaction mixture was heated to 80° C. for 16 h. Progress of the reaction was monitored by TLC. The reaction mixture was cooled to 25° C., diluted with ethyl acetate (25 ml) and filtered through a plug of celite and concentrated to give crude product. The crude product was purified over silica gel (100-200 mesh) by column chromatography using 30% ethyl acetate in hexane as eluent to obtain the title compound (0.8 g, 27.2%).
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