[C:1]([CH2:3][C:4]([OH:6])=O)#[N:2].C(Cl)(=O)C(Cl)=O.[NH2:13][C:14]1[C:19]([F:20])=[CH:18][C:17]([Cl:21])=[CH:16][C:15]=1[C:22]([C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1)=O.C(N(CC)CC)C>ClCCl.CN(C=O)C.O.C1(C)C=CC=CC=1>[Cl:21][C:17]1[CH:16]=[C:15]2[C:14](=[C:19]([F:20])[CH:18]=1)[NH:13][C:4](=[O:6])[C:3]([C:1]#[N:2])=[C:22]2[C:24]1[CH:25]=[CH:26][CH:27]=[CH:28][CH:29]=12-Cyanoacetic acid (140 mg, 1.65 mmol) was co-evaporated with toluene two times and then suspended in dichloromethane (3 ml). One drop of DMF was added followed by dropwise addition of oxalyl chloride (304 mg, 206 μl, 2.4 mmol) at 0° C. The reaction mixture was stirred for 15 min at 0° C. and for another 2.5 h at room temperature. The solvent was then removed and the remaining residue was co-evaporated two times with dichloromethane. The residue was again dissolved in dichloromethane (3 ml) and a solution of (2-amino-5-chloro-3-fluoro-phenyl)-phenyl-methanone (374 mg, 1.5 mmol) and triethylamine (152 mg, 209 μl, 1.5 mmol) in dichloromethane (3 ml) was added dropwise at 0° C. The mixture was stirred at room temperature overnight. Then triethylamine (227 mg, 313 μl, 2.25 mmol) was added dropwise and the reaction mixture was stirred for 2 h before dichloromethane and water were added and the phases were separated. The aqueous layer was extracted with dichloromethane and the combined organic layers were washed with water and brine, dried with Na2SO4 and evaporated. The remaining residue was purified by column chromatography (silica gel, heptane/EtOAc 80:20-45:55) to afford the title compound (146 mg, 33%) as white solid. MS (ESI): 299.3 (M+H)+.
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