反应详情

3-(4-(3-(2,6-difluorophenyl)ureido)-3-methylphenyl)isoxazole-5-carboxylic acid (1.0 equiv.) was dissolved in 25 ml of DMF, N,N′-dicyclocarbodiimide (1.2 equiv.) and 1-hydroxybenzotriazole (1.0 equiv.) was added and stirred at room temperature for 10 min. L-valine methyl ester hydrochloride (1.5 equiv.) was neutralized with triethylamine (1.5 equiv.) in 10 ml of DMF and was added to the above mixture and the resulting reaction mixture was stirred at room temperature for 48 hours. DMF was evaporated and then diluted with EtOAc. The organic layer was washed with water, brine, dried over Na2SO4, filtered and concentrated in vacuo. The residue was dissolved in a chloroform and methanol mixture, adsorbed on silica (100-200 mesh) and purified by flash chromatography on silica gel, and then eluted with 0-2% methanol in chloroform to obtain a crude product.

1. additionwas added to the above mixture
2. customthe resulting reaction mixture
3. stirringwas stirred at room temperature for 48 hours
4. customDMF was evaporated
5. additiondiluted with EtOAc
6. washThe organic layer was washed with water, brine
7. dry with materialdried over Na2SO4
8. filtrationfiltered
9. concentrationconcentrated in vacuo
10. dissolutionThe residue was dissolved in a chloroform and methanol mixture
11. custompurified by flash chromatography on silica gel
12. washeluted with 0-2% methanol in chloroform