3.4. General Synthesis Procedure for Substituted 2-Aminopyrimidines Id–f

Intermediates Id–f were prepared by a method similar to that for intermediates Ia–c. A solution of NaH (5.8 mmol) in dry THF (12 mL) was cooled to 0 °C under N₂, then a substituted alcohol (6.1 mmol) was added dropwise. The mixture was stirred for 15 min while maintaining the temperature at 0 °C. Next, 2-amino-4-chloro-6- substituted-pyrimidine (5.8 mmol) was added to the solution. The reaction was continued at 62 °C for 15 h. Then the mixture was cooled to ambient temperature, and quenched with 1 mL of 1 M hydrochloric acid solution. The mixture was diluted with EtOAc (20 mL), washed twice with a saturated NaHCO₃ solution (20 mL) and brine (20 mL), dried with anhydrous Na₂SO₄ and evaporated in vacuo. Finally, the residue was purified by silica gel column chromatography (EtOAc/petroleum ether) to afford compounds Id–f.

4-Chloro-6-methoxypyrimidin-2-amine (Id). White solid, mp 165–167 °C, yield = 84%. ¹H-NMR (CDCl₃) δ 6.04 (s, 1H, ArH), 5.35–5.14 (m, 2H, NH₂), 3.81 (s, 3H, OCH₃).

4-Methyl-6-(2,2,2-trifluoroethoxy)pyrimidin-2-amine (Ie). White solid, mp 109–111 °C, yield = 69%. ¹H-NMR (CDCl₃) δ 6.42 (s, 1H, ArH), 5.50 (s, 2H, NH₂), 4.60 (q, J = 8.4 Hz, 2H, OCH₂CF₃), 2.18 (s, 3H, CH₃).

4-Chloro-6-(2,2,2-trifluoroethoxy)pyrimidin-2-amine (If). White solid, mp 82–83 °C, yield = 76%. ¹H-NMR (CDCl₃) δ 6.23 (s, 1H, ArH), 5.59 (s, 2H, NH₂), 4.70 (q, J = 8.4 Hz, 2H, OCH₂CF₃).