To a mixture of (R)-3-(piperazin-1-yl)cyclopent-1-enecarbonitrile (0.500 g, 2.82 mmol), 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene (XANTPHOS) (0.326 g, 0.564 mmol), palladium (II) acetate (Pd(OAc)2) (63.3 mg, 0.282 mmol) and cesium carbonate (1.838 g, 5.64 mmol) in toluene (15 ml) was added 4-bromo-2-fluoro-N-methylbenzamide (WO2006064251, 0.500 g, 2.82 mmol). The reaction mixture was heated to 110° C. for 16 h. The progress of the reaction was monitored by TLC. The reaction mixture was cooled to 25° C. and filtered through celite. The filtrated was concentrated under reduced pressure to obtain a crude product, which was purified by column chromatography over silica gel (100-200 mesh) using 1-5% methanol in dichloromethane as an eluent to obtain the title compound (0.270 g, 29.1%).
