反应详情

温度

0 °C

To a solution of 4,6-dimethoxy-2-methyl nicotinamide (2.0 g, 10.2 mmol) in THF (80 mL), n-butyl lithium (19.12 mL, 30.6 mmol, 1.6 M solution in hexane) was added slowly under nitrogen at −78° C. After completion of addition the mixture was stirred for 1 h at 0° C. Then cooled to −78° C. and a solution of 4-methoxy benzonitrile (1.65 g, 10.2 mmol) in THF (10 mL) was added quickly. The cooling bath was removed and the reaction mixture was allowed to warm to room temperature and stirred for 16 h at room temperature. Saturated NH4Cl solution was added with cooling. The organic layer was washed with water, brine, dried over Na2SO4 and concentrated to give crude product. The crude product was purified by chromatography using 50% ethyl acetate in hexane and then 2% methanol in ethyl acetate to give 2,4-dimethoxy-7-(4-methoxy-3,5-dimethylphenyl)-1,6-naphthyridin-5(6H)-one (410 mg, 12%), as a yellow solid. Selected data: MS (ES) m/z: 341.1; mp 262-263° C. (at decomposition).

1. additionAfter completion of addition the mixture
2. temperatureThen cooled to −78° C.
3. customThe cooling bath was removed
4. temperatureto warm to room temperature
5. stirringstirred for 16 h at room temperature
6. additionSaturated NH4Cl solution was added
7. temperaturewith cooling
8. washThe organic layer was washed with water, brine
9. dry with materialdried over Na2SO4
10. concentrationconcentrated
11. customto give crude product
12. customThe crude product was purified by chromatography