[Synthesis]
5-Hydroxy-2-(hydroxymethyl)-4H-pyran-4-one (tricarboxylic acid) (0.55 g, 3.87 mmol) was used as starting material, which was dissolved in thionyl chloride (5 mL, 68.5 mmol), and stirred for 3 hours at room temperature. After completion of the reaction, the excess thionyl chloride was removed by distillation under reduced pressure to afford 2-(chloromethyl)-5-hydroxy-4H-pyran-4-one (0.61 g, 98% yield), the product was an off-white solid.1H NMR (500 MHz, DMSO-d6) δ: 8.13 (s, 1H), 6.57 (s, 1H), 4.66 (s, 2H).
Step 2: Pyrimidine-2-thiol (161 mg, 1.433 mmol) was dissolved in 2 mL of methanol, sodium methanol solution (310 mg, 1.433 mmol) was added and stirred until completely dissolved. Acetonitrile (10 mL) and 2-(chloromethyl)-5-hydroxy-4H-pyran-4-one (230 mg, 1.433 mmol) were then added and stirred for 3 h at room temperature. The completion of the reaction was confirmed by LC/MS analysis. The solvent was removed under reduced pressure to afford the crude product 5-hydroxy-2-((pyrimidin-2-ylthio)methyl)-4H-pyran-4-one (406 mg, 96% yield) and an equimolar amount of NaCl, the product was a yellow solid, which could be used in the next reaction without further purification.1H NMR (500 MHz, CDCl3) δ: 8.52 (d, 2H, J=4.9 Hz) , 7.80 (s, 1H), 7.02 (t, 1H, J=4.8Hz), 6.63 (s, 1H), 4.23 (s, 2H).
Step 3: 5-Hydroxy-2-((pyrimidin-2-ylthio)methyl)-4H-pyran-4-one (200 mg, 0.847 mmol), cesium carbonate (276 mg, 0.847 mmol), and 4-nitrobenzoyl chloride (220 mg, 1.185 mmol) were dissolved in acetonitrile (8 mL) and stirred overnight at room temperature. After the reaction was complete, the solvent was removed under reduced pressure to give a light yellow solid. The solid was partitioned with about 20 mL of 1:1 ethyl acetate and water. The target product, 4-oxo-6-((pyrimidin-2-ylthio)methyl)-4H-pyran-3-yl 4-nitrobenzoate, was insoluble in both phases and was collected by filtration. The solid was dried in vacuum to afford the target product (202 mg, 62% yield) as a brown solid.1H NMR (500 MHz, DMSO-d6) δ: 8.69 (d, 2H, J=4.8 Hz), 8.68 (s, 1H), 8.40 (d, 2H, J=8.8 Hz), 8.29 (d, 2H, J=8.8 Hz), 7.29 ( t, 1H, J=4.9Hz), 6.65 (s, 1H), 4.45 (s, 2H).13C NMR (125 MHz, DMSO-d6) δ: 171.2, 168.8, 165.9, 161.7, 158.1, 150.8, 149.9, 140.3, 133.0, 131.4, 124.2 118.0, 114.6, 31.2. |