反应详情

温度

102.5 °C

3-Chloro-2,5-pentanedione (2) (106 mL, 119 g, 887 mmol, 1.2 eq) was dissolved in 650 mL of anhydrous ethanol. 2-Aminopyrimidine (1) (71.5 g×97%=69.36 g, 729 mmol) was added to above stirred solution. The resulting mixture was refluxed for 40 h at an oil bath temperature of 100-105° C. The black reaction mixture was cooled and concentrated under reduced pressure. The residue was treated with saturated sodium bicarbonate solution (˜500 mL) in portions, and swelled the flask to mix well. The mixture was extracted with dichloromethane (×6). The extracts were washed with sodium bicarbonate solution and brine. The organic phase was dried and concentrated. The residue was purified by flash chromatography on a silica gel column (7×30 cm) by gradient elution using n-hexane-ethyl acetate (3:1, 2:1, 1:1, 1:2 and 0:1) and then dichloromethane-methanol (30:1, 20:1, 10:1 and 5:1). The product fractions were collected (TLC, Rf 0.36, 100% ethyl acetate) and concentrated providing a light black solid. Other fractions contained products were collected and re-purified again by the same way. 27.84 g (21.8%) of the final product was obtained. Portion of the product was re-crystallized from small amount of acetonitrile to give red to light brown crystals 4, m.p. 255.6-256.6° C. 1H NMR (CDCl3) δ 2.65 (s, 3H, 3-COCH3), 2.86 (s, 3H, 2-CH3), 7.04-7.12 (m, 1H, 6-H), 7.70-7.74 (m, 1H), 9.96-10.00 (m, 1H).

1. customThe black reaction mixture
2. temperaturewas cooled
3. concentrationconcentrated under reduced pressure
4. additionThe residue was treated with saturated sodium bicarbonate solution (˜500 mL) in portions
5. additionto mix well
6. extractionThe mixture was extracted with dichloromethane (×6)
7. washThe extracts were washed with sodium bicarbonate solution and brine
8. customThe organic phase was dried
9. concentrationconcentrated
10. customThe residue was purified by flash chromatography on a silica gel column (7×30 cm) by gradient elution
11. customThe product fractions were collected (TLC, Rf 0.36, 100% ethyl acetate)
12. concentrationconcentrated
13. customproviding a light black solid
14. customwere collected
15. customre-purified again by the same way