The general procedure for the synthesis of 2,4-bis(4-morpholinyl)-6-chloropyrimidine from morpholine (12.6 mL, 144 mmol) and 2,4,6-trichloropyrimidine (4.4 g, 24 mmol) was as follows: first, the morpholine was dissolved in a mixture of toluene (22 mL) and water (8.8 mL) as solvent. Subsequently, 2,4,6-trichloropyrimidine was dissolved in toluene (22 mL) and slowly added dropwise to the morpholine solution. The reaction mixture was stirred and heated to 83°C at room temperature and maintained for 3 hours. After completion of the reaction, it was cooled to room temperature and phase separation was carried out. The organic phase was washed with 10 mol/L hydrochloric acid and then dried with anhydrous sodium sulfate. The crude product was purified by silica gel column chromatography, and the eluent was a mixed solvent of petroleum ether and ethyl acetate (1:1, v/v), which ultimately afforded 2,4-bis(4-morpholinyl)-6-chloropyrimidine (6.68 g, 98% yield).
