反应详情

温度

100 °C

To 4-(2-amino-6-methyl-4-pyrimidinyl)-2,6-difluorobenzaldehyde (4.0 g, 16.1 mmol) in water (150 mL) and EtOH (50 mL) were added hydroxylamine hydrochloride (1.23 g, 17.7 mmol) and sodium carbonate (1.87 g, 17.7 mmol). The mixture was stirred for 3 hours at 100° C. The reaction mixture was filtered and the solid was washed with water. The combined filtrate was extracted with EtOAc, and the organic layer was washed with brine, dried (MgSO4), filtered and concentrated. The resulting solid was combined with the solid obtained after filtration of the reaction mixture and treated with acetic anhydride (used as solvent) into a sealable tube. The tube was sealed and the reaction mixture was stirred for 5 days at 100° C. LCMS analysis showed a mixture of mono and bis-acetylated desired product together with their respective acetylated oximes. The reaction mixture was heated for 2 more days at 110° C. The mixture was concentrated and the resulting residue was treated with CH3OH. The mixture was filtered and the solid was washed with more CH3OH to provide the title compound (1.3 g) as a tan solid. To the filtrate solution (150 mL) containing mostly bis-acetylated desired product was added K2CO3 (˜1 g) and the reaction mixture was stirred overnight at room temperature. More K2CO3 (˜1 g) was added followed by water (˜50 mL) and the reaction mixture was stirred overnight at room temperature. LCMS analysis showed complete conversion to the mono-acetylated product. The reaction mixture was diluted with water and filtered. The resulting solid was washed with CH3OH to provide the title compound (1.03 g) as a brown solid. LC-MS (ES) m/z=289 [M+H]+.

1. filtrationThe reaction mixture was filtered
2. washthe solid was washed with water
3. extractionThe combined filtrate was extracted with EtOAc
4. washthe organic layer was washed with brine
5. dry with materialdried (MgSO4)
6. filtrationfiltered
7. concentrationconcentrated
8. customobtained
9. filtrationafter filtration of the reaction mixture
10. additiontreated with acetic anhydride (used as solvent) into a sealable tube
11. customThe tube was sealed
12. stirringthe reaction mixture was stirred for 5 days at 100° C
13. additiona mixture of mono and bis-acetylated desired product together with their respective acetylated oximes
14. temperatureThe reaction mixture was heated for 2 more days at 110° C
15. concentrationThe mixture was concentrated
16. additionthe resulting residue was treated with CH3OH
17. filtrationThe mixture was filtered
18. washthe solid was washed with more CH3OH