GENERAL PROCEDURE: Intermediate Id-f was prepared similarly to Intermediate Ia-c. Anhydrous tetrahydrofuran (12 mL) solution of sodium hydride (5.8 mmol) was cooled to 0 °C under nitrogen protection, followed by slow dropwise addition of substitutional alcohol (6.1 mmol). The reaction mixture was kept stirred at 0 °C for 15 min. Then, 2-amino-4,6-dichloropyrimidine (5.8 mmol) was added to the reaction system. The reaction temperature was raised to 62°C and the reaction was continued for 15 hours. After completion of the reaction, the mixture was cooled to room temperature and the reaction was quenched with 1 M hydrochloric acid solution (1 mL). The reaction mixture was diluted with ethyl acetate (20 mL), washed twice sequentially with saturated sodium bicarbonate solution (20 mL) and brine (20 mL), and the organic phase was dried with anhydrous sodium sulfate and concentrated under reduced pressure. Finally, the residue was purified by silica gel column chromatography (ethyl acetate/petroleum ether as eluent) to afford the target compound Id-f. 4-Chloro-6-methoxypyrimidin-2-amine (Id) was a white solid with a melting point of 165-167 °C in 84% yield.1H-NMR (CDCl3) δ 6.04 (s, 1H, ArH), 5.35-5.14 (m, 2H , NH2), 3.81 (s, 3H, OCH3).
