反应详情

温度

-78 °C

To a suspension of (4-aminophenyl)(morpholino)methanone (9.02 g, 43.8 mmol) in THF (20 mL) was added lithium bis(trimethylsilyl)amide (66.7 mL, 66.7 mmol, 1M solution in THF) dropwise over 15 min. at −78° C. under nitrogen. The reaction mixture was stirred for one hour at −78° C. To the resulting brown solution was added a solution of 2,6-dichloronicotinic acid (4 g, 20.83 mmol) in THF (12 ml) dropwise at −78° C. The reaction mixture was removed from the dry ice bath and stirred overnight at rt. The resulting dark solids were washed with a small amount of THF to remove (4-aminophenyl)(morpholino)methanone on the surface, followed by the addition of water and 18 ml of 6N HCl (pH of 2). The solids were filtered and the resulting pink filter cake was washed with water (˜1 i) until the filter cake was white powder and the filtrate was colorless. The filter cake was transferred to a flask with MeOH and CH2Cl2, and dried on a rotary evaporator with MeOH to give 6.60 g of 6-chloro-2-(4-(morpholine-4-carbonyl)phenylamino)nicotinic acid as a white solid.

1. customThe reaction mixture was removed from the dry ice bath
2. stirringstirred overnight at rt
3. washThe resulting dark solids were washed with a small amount of THF
4. customto remove (4-aminophenyl)(morpholino)methanone on the surface
5. additionfollowed by the addition of water and 18 ml of 6N HCl (pH of 2)
6. filtrationThe solids were filtered
7. washthe resulting pink filter cake was washed with water (˜1 i) until the filter cake
8. customThe filter cake was transferred to a flask with MeOH and CH2Cl2
9. dry with materialdried on a rotary evaporator with MeOH