1-(2-Chloropyrimidin-4-yl)-3-methyl-1H-pyrazole-4-carbaldehyde was synthesized in the following steps:
1. Preparation of Intermediate 1: 3-methyl-1H-pyrazole-4-carboxaldehyde (6.4 g, 58.0 mmol) was dissolved in 60 mL of anhydrous N,N-dimethylformamide (DMF) under nitrogen protection, followed by addition of potassium carbonate (10.8 g, 77.8 mmol) and 2,4-dichloropyrimidine (8.64 g, 58.0 mmol). The reaction mixture was stirred at room temperature for 14 h. The reaction process was monitored by LC-MS or thin layer chromatography (TLC).
2. Post-treatment: After completion of the reaction, the mixture was diluted with ethyl acetate and washed twice with saturated saline. The organic layers were combined, dried with anhydrous sodium sulfate, filtered and concentrated under reduced pressure to remove the solvent.
3. Purification: The crude product was purified by silica gel column chromatography, the eluent was a mixed solvent of heptane and ethyl acetate, the target product 1-(2-chloropyrimidin-4-yl)-3-methyl-1H-pyrazole-4-carbaldehyde (Intermediate 1) was obtained as a white solid (5.47 g, 42% yield).
Product characterization: MS (ESI) m/z 223 [M + H]+; 1H NMR (300 MHz, CDCl3) δ 10.06 (s, 1H), 9.04 (s, 1H), 8.70 (d, 1H, J = 5.4 Hz), 7.87 (d, 1H, J = 5.4 Hz), 2.59 (s, 3H).
