反应详情

温度

94 °C

DABCO (121 mg) was added to a solution of ethyl 3-[7-(5-{3-chloro-4-[(1-methylethyl)oxy]phenyl}-1,2,4-oxadiazol-3-yl)-4-fluoro-1H-indol-3-yl]propanoate (D46) (340 mg) in DMF (2 mL) and dimethyl carbonate (2 mL). The reaction mixture was stirred at 94° C. for 3 days. Then the reaction was quenched with water, and extracted with EtOAc for 3 times. The combined organic solution was washed with brine, and dried over anhydrous sodium sulfate. The dried solution was concentrated to afford the crude product as a yellow solid. This solid was dissolved in THF (3 mL) and water (3 mL). Sodium hydroxide (40 mg) was then added to the mixture. The reaction mixture was stirred at 90° C. for 1 h. Then 0.5 M HCl was added until pH was about 6. The solvent was concentrated, and the residue was dissolved in water. The precipitated solid was purified by Mass Directed Auto Prep to afford 3-[7-(5-{3-chloro-4-[(1-methylethyl)oxy]phenyl}-1,2,4-oxadiazol-3-yl)-4-fluoro-1-methyl-1H-indol-3-yl]propanoic acid (E20) (83 mg) as a white solid. δH (DMSO-d6, 400 MHz): 1.35 (6H, d), 2.59 (2H, t), 3.03 (2H, t), 3.62 (3H, s), 4.88 (1H, m), 6.95 (1H, dd), 7.22 (1H, s), 7.42 (2H, m), 8.12 (1H, dd), 8.19 (1H, d), 12.14 (1H, br s). δF (DMSO-d6, 376 MHz): −120.6. MS (ES): C23H21ClFN3O4 requires 457; found 458.1 (M+H+).

1. customThen the reaction was quenched with water
2. extractionextracted with EtOAc for 3 times
3. washThe combined organic solution was washed with brine
4. dry with materialdried over anhydrous sodium sulfate
5. concentrationThe dried solution was concentrated
6. customto afford the crude product as a yellow solid
7. stirringThe reaction mixture was stirred at 90° C. for 1 h
8. concentrationThe solvent was concentrated
9. dissolutionthe residue was dissolved in water
10. customThe precipitated solid was purified by Mass Directed Auto Prep