4-Chloroaniline → N-(4-chloro-phenyl)-4-(2-chloro-pyrimidin-4-yl)-benzamide

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Reaction Steps

The crude 4-(2-hydroxy-pyrimidin-4-yl)-benzoic acid is treated with POCl3 (4 mL) at 100° C. for 14 h and cooled down to room temperature. POCl3 is removed under vacuum and the residue is flushed once with toluene (3 mL). The residue is dissolved in anhydrous dichloromethane (4 mL) and put into ice bath. 4-Chloroaniline (790 mg, 6.28 mmol) is added followed by the addition of Et3N (1.2 g, 12 mmol). After stirring at 0° C. for 1 h, the mixture is poured into water (100 mL) and extracted with EtOAc (3×50 mL). The combined extracts is washed with brine, dried (MgSO4) and concentrated. The residue is purified by flash column chromatography (silica gel, 0-80% EtOAc/hexane) to provide the desired N-(4-chloro-phenyl)-4-(2-chloro-pyrimidin-4-yl)-benzamide as yellow solid (650 mg, 44%). HPLC-MS calculated C17H11Cl2N3O (M+1+): 344.0. Found: 344.0.

Provenance & Evidence