Thionyl Chloride → 4-Chloro-N-(4-chloro-6-methoxy-5-pyrimidinyl)-3-cyanobenzamide

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Reaction Steps

To a suspension of the above-mentioned 4-chloro-3-cyanobenzoic acid (1.20 g, 6.61 mmol) in dry benzene (10 mL) was added thionyl chloride (0.58 mL, 7.95 mmol). The mixture was heated under refluxing for 4 hours, and then placed under reduced pressure to distill the solvent off. To the residue was added dry dichloromethane (5 mL), and the mixture was placed under reduced pressure to distill the dry benzene and the remaining thionyl chloride off. The residue was dissolved in dry dichloromethane (45 mL). The resulting solution was dropwise added under ice-cooling to a solution of 5-amino-4-chloro-6-methoxypyrimidine (2.11 g, 13.2 mmol) in dry dichloromethane (45 mL) for 5 minutes. The mixture was stirred at room temperature for 115 hours. The precipitated crystalline product was collected by filtration, washed with dichloromethane (5 mL×2), and placed under reduced pressure to distill the solvent off. The residue was repeatedly purified by silica gel column chromatography (methanol/chloroform), to obtain 1.61 g (yield 75%) of the titled compound as a pale brown crystalline product.

Provenance & Evidence