2-Chloro-5-methoxypyrimidin-4-amine was synthesized as follows: 2,4-dichloro-5-methoxypyrimidine (10 g, 56.17 mmol) was dissolved in 1,4-dioxane (20 mL) under argon protection and stirred at room temperature. Subsequently, ammonium hydroxide (25.5 mL) was slowly added to the solution. The reaction mixture was transferred to a sealed tube, heated to 100 °C and maintained for 21 hours. The reaction process was monitored by thin layer chromatography (TLC). Upon completion of the reaction, the volatile components were evaporated under reduced pressure. The crude product was purified by silica gel column chromatography with 40% ethyl acetate/hexane as eluent to afford 2-chloro-5-methoxypyrimidin-4-amine (8.9 g, 99% yield) as an off-white solid. The structure of the product was confirmed by 1H-NMR (DMSO-d6, 500MHz): δ7.68 (s, 1H), 3.81 (s, 3H); LC-MS (column: X-Bridge C-18, 50×3.0 mm, 3.5 μm; mobile phase: 0.05% aqueous trifluoroacetic acid/acetonitrile; flow rate: 0.80 mL/min) showed m/z 160 ([M+H]+), retention time 2.18 min; TLC (unfolding agent: 50% ethyl acetate/hexane) showed an Rf value of 0.3.
