反应详情

A solution of 1-(2-{[2-(methyloxy)ethyl]oxy}phenyl)-3-{3-methyl-4-[(phenylmethyl)oxy]phenyl}propane-1,3-dione (0.24 g, 0.56 mmol), urea (0.34 g, 5.6 mmol), 4.0M hydrochloric acid in dioxane (1.4 mL, 5.6 mmol) in ethanol (2 mL) was heated in a 110° C. oil bath for 12 h. The solution was allowed to cool to room temperature and was concentrated in vacuo. The residue was partitioned between ethyl acetate (10% methanol) and aqueous saturated sodium bicarbonate. The layers were separated and the aqueous layer was extracted with ethyl acetate (2×). The combined organic layers were dried over anhydrous sodium sulfate, filtered and concentrated in vacuo. This crude mixture was taken up in 2.0 mL trifluoroacetic acid and heated in an 80° C. oil bath for 1 hour then concentrated. Purification of the residue by HPLC (reverse-phase, acetonitrile/water with 0.1% trifluoroacetic acid), followed by concentration in vacuo, treatment with methanol and 4.0 M hydrochloric acid in dioxane, and lyophilization gave the title compound 4-(4-hydroxy-3-methylphenyl)-6-(2-{[2-(methyloxy)ethyl]oxy}phenyl)pyrimidin-2(1H)-one hydrochloride (0.037 g, 19%). 1H NMR (400 MHz, d6-DMSO): 11.07 (s, 1H), 8.01 (d, 1H), 7.92 (dd, 1H), 7.74 (dd, 1H), 7.63 (dt, 1H), 7.47 (s, 1H), 7.29 (d, 1H), 7.19 (dt, 1H), 7.10 (d, 1H), 4.29 (m, 2H), 3.71 (m, 2H), 3.27 (s, 3H), 2.20 (s, 3H). MS (EI) for C20H20N2O4: 352 (MH+).

1. concentrationwas concentrated in vacuo
2. customThe residue was partitioned between ethyl acetate (10% methanol) and aqueous saturated sodium bicarbonate
3. customThe layers were separated
4. extractionthe aqueous layer was extracted with ethyl acetate (2×)
5. dry with materialThe combined organic layers were dried over anhydrous sodium sulfate
6. filtrationfiltered
7. concentrationconcentrated in vacuo
8. temperatureheated in an 80° C. oil bath for 1 hour
9. concentrationthen concentrated
10. customPurification of the residue by HPLC (reverse-phase, acetonitrile/water with 0.1% trifluoroacetic acid)
11. concentrationfollowed by concentration in vacuo, treatment with methanol and 4.0 M hydrochloric acid in dioxane, and lyophilization