反应详情

A stirred solution of 6-chloro-4-(isopropylamino)nicotinic acid (2) in DCM (15 mL) was cooled to 0° C., oxalyl chloride (2 equiv) was added, followed by addition of 2 drops of DMF. The reaction mixture was stirred at room temperature for 2 h. The reaction mixture was concentrated to remove excess of oxalyl chloride. The acyl chloride, generated in-situ was dissolved in THF and added dropwise to a cool, stirred solution of ethyl 2-amino-3-oxobutanoate (1.1 equiv.) and NMM (5 equiv.) in THF. The reaction temperature was slowly brought to room temperature and stirred overnight. The reaction mixture was diluted with EtOAc and washed with water, followed by brine solution. The EtOAc layer was collected, dried over Na2SO4, filtered and concentrated. The crude material obtained was purified by column chromatography through silica gel and EtOAc: Pet. Ether as eluent to afford the title compound, ethyl 2-(6-chloro-4-(isopropylamino)nicotinamido)-3-oxobutanoate.

1. concentrationThe reaction mixture was concentrated
2. customto remove excess of oxalyl chloride
3. dissolutionin-situ was dissolved in THF
4. additionadded dropwise to a cool
5. customwas slowly brought to room temperature
6. stirringstirred overnight
7. washwashed with water
8. customThe EtOAc layer was collected
9. dry with materialdried over Na2SO4
10. filtrationfiltered
11. concentrationconcentrated
12. customThe crude material obtained
13. customwas purified by column chromatography through silica gel and EtOAc