反应详情

温度

80 °C

Chloroacetaldehyde (50% aqueous solution, 0.70 mL, 5.7 mmol) was added to a suspension of 6-amino-4-(4-bromo-2-chlorophenylamino)-5-chloronicotinic acid methyl ester (28) in DMF (7 mL) contained in a sealed tube. The reaction mixture was heated at 80° C. for four hours and then allowed to cool to room temperature and stir overnight. The dark brown solution was diluted with water (70 mL) the resulting light brown precipitate was collected by filtration and washed with water. The solids were dissolved into THF. Two volumes of ethyl acetate were added and the organic solution washed with brine, dried over NaSO4, filtered, and concentrated in vacuo to provide a brown solid. The aqueous filtrate was extracted with ethyl acetate and the organic extracts were dried over NaSO4, filtered, and concentrated in vacuo. This material was combined with the previously isolated brown solid and the combined material subjected to column chromatography (dichloromethane, followed by 20:1 dichloromethane/methanol). The desired product (29) was isolated as a light yellow solid (0.752 g, 64%). MS (APCI+) m/z 414, 416, 418 (M+; Cl, Br pattern) detected.

1. customcontained in a sealed tube
2. temperatureto cool to room temperature
3. filtrationwas collected by filtration
4. washwashed with water
5. dissolutionThe solids were dissolved into THF
6. additionTwo volumes of ethyl acetate were added
7. washthe organic solution washed with brine
8. dry with materialdried over NaSO4
9. filtrationfiltered
10. concentrationconcentrated in vacuo
11. customto provide a brown solid
12. extractionThe aqueous filtrate was extracted with ethyl acetate
13. dry with materialthe organic extracts were dried over NaSO4
14. filtrationfiltered
15. concentrationconcentrated in vacuo