反应详情

温度

-10 °C

To a −78° C. solution of 3.9 g (32.1 mmol) of 4-amino-2,6-dimethylpyridine in 120 mL of THF was added dropwise 17.5 mL (30.5 mmol) of 1.6 M n-butyllithium in hexanes. The reaction solution was stirred for 15 minutes at which time 3.0 g (8.0 mmol) of the product of Example 7, 6-(3,5-dimethoxy-phenyl)-8-ethyl-2-methanesulfinyl-8H-pyrido[2,3-d]pyrimidin-7-one, was added in small portions as a solid. The reaction mixture was allowed to warm slowly to −10° C. then remain at −10° C. overnight. The reaction. mixture was poured into ethyl acetate/water/5 mL 6N HCl. The mixture was shaken and separated. The organic phase was washed with a saturated solution of sodium bicarbonate, twice with water, and brine, then dried over magnesium sulfate, filtered, and concentrated to a solid residue. The residue was triturated under ethyl acetate/dichloromethane. The resulting material was further purified by column chromatography eluting with 5:50:50 methanol/ethyl acetate/dichloromethane to give an orange crystalline material. This material was dissolved in 150 mL of hot 1:9 methanol/chloroform and filtered. The addition of 60 mL of hexane results in the precipitation of 0.99 g (28%) of the title compound as a pale yellow solid.

1. additionwas added in small portions as a solid
2. customThe reaction
3. customseparated
4. washThe organic phase was washed with a saturated solution of sodium bicarbonate, twice with water, and brine
5. dry with materialdried over magnesium sulfate
6. filtrationfiltered
7. concentrationconcentrated to a solid residue
8. customThe residue was triturated under ethyl acetate/dichloromethane
9. customThe resulting material was further purified by column chromatography
10. washeluting with 5:50:50 methanol/ethyl acetate/dichloromethane
11. customto give an orange crystalline material
12. filtrationfiltered
13. additionThe addition of 60 mL of hexane