反应详情

To the solution of 3-chloro-4-[(1-methylethyl)oxy]benzoic acid (D32) (676 mg) in tetrahydrofuran (50 mL) were added EDCI (824 mg) and HOBT (658 mg). The resulting solution was stirred at room temperature for 1 hour. Then ethyl 3-{6-fluoro-7-[(Z)-(hydroxyamino)(imino)methyl]-1H-indol-3-yl}propanoate (D145) (840 mg) was added and the solution was stirred at room temperature for another 2 hours. THF was removed in vacuo and the residue was dissolved in ethyl acetate (50 mL), washed with water (2×10 mL) and dried over sodium sulphate. The organic phase was concentrated. The residue was dissolved in THF (3 mL), TBAF (3 g) was added and the reaction solution was stirred under microwave (120° C., 2.5 hours). The reaction solution was poured into ethyl acetate (100 mL), washed with water (3×20 mL), dried over sodium sulphate. The organic phase was concentrate and the residue was purified by column chromatography to afford ethyl 3-[7-(5-{3-chloro-4-[(1-methylethyl)oxy]phenyl}-1,2,4-oxadiazol-3-yl)-6-fluoro-1H-indol-3-yl]propanoate (D146) (640 mg) as an off white solid. MS (ES): C24H23ClFN3O4 requires 471; found 472.2 (M+H+).

1. stirringthe solution was stirred at room temperature for another 2 hours
2. customTHF was removed in vacuo
3. dissolutionthe residue was dissolved in ethyl acetate (50 mL)
4. washwashed with water (2×10 mL)
5. dry with materialdried over sodium sulphate
6. concentrationThe organic phase was concentrated
7. dissolutionThe residue was dissolved in THF (3 mL)
8. additionTBAF (3 g) was added
9. stirringthe reaction solution was stirred under microwave (120° C., 2.5 hours)
10. additionThe reaction solution was poured into ethyl acetate (100 mL)
11. washwashed with water (3×20 mL)
12. dry with materialdried over sodium sulphate
13. concentrationThe organic phase was concentrate
14. customthe residue was purified by column chromatography