COC([C:5]1([NH2:10])[NH:9][CH:8]=[CH:7][S:6]1)=O.Cl[CH2:12][CH2:13][N:14]([CH2:27][CH2:28]Cl)[C:15](=[O:26])[C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][C:17]=1[C:22]([F:25])([F:24])[F:23].[C:30]([O-:33])([O-])=[O:31].[K+].[K+].[Na+].[I-].[CH3:38]OCCOC>>[CH3:38][O:33][C:30]([C:7]1[S:6][C:5]([N:10]2[CH2:28][CH2:27][N:14]([C:15](=[O:26])[C:16]3[CH:21]=[CH:20][CH:19]=[CH:18][C:17]=3[C:22]([F:25])([F:24])[F:23])[CH2:13][CH2:12]2)=[N:9][CH:8]=1)=[O:31]A reaction mixture of 2-aminothiazole-2-carboxylic acid methyl ester (0.790 g, 5.0 mmol), N,N-bis(2-chloroethyl)-2-trifluoromethylbenzamide (1.880 g, 6 mmol), K2CO3 (1.0 g, 7.2 mmol), and NaI (0.2 g) in 1,2-dimethoxyethane (20 mL) was heated to reflux for 24 hours. The solvent was removed by evaporation, and the residue was dissolved in ethyl acetate, washed with water and brine, dried over anhydrous Na2SO4 and concentrated. The residue was purified by column chromatography to give 2-[4-(2-trifluoromethylbenzoyl)piperazin-1-yl]thiazole-5-carboxylic acid methyl ester (0.317 g) which was used for next step without further purification.
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