反应详情

温度

70 °C

DABCO (111 mg) was added to a solution of 3-[7-(5-{5-chloro-6-[(1-methylethyl)oxy]-3-pyridinyl}-1,2,4-oxadiazol-3-yl)-1H-indol-3-yl]propanoic acid (E13) (100 mg) in dimethyl carbonate (3 mL) and DMF (2 mL). The resulting mixture was heated at reflux for 5 days. After cooling, 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. The residue was dissolved in THF (3 mL) and water (3 mL). Sodium hydroxide (40 mg) was added to the mixture. The resulting mixture was heated at 70° C. for 40 mins. Then 0.5 M HCl solution was added until pH was about 6. The solvent was concentrated, and the residue was dissolved in water. The precipitate was purified by Mass Directed Auto Prep to afford 3-[7-(5-{5-chloro-6-[(1-methylethyl)oxy]-3-pyridinyl}-1,2,4-oxadiazol-3-yl)-1-methyl-1H-indol-3-yl]propanoic acid (E14) (18 mg) as a white solid. δH (DMSO-d6, 400 MHz): 1.38 (6H, d), 2.60 (2H, t), 2.96 (2H, t), 3.62 (3H, s), 5.44 (1H, m), 7.17 (1H, t), 7.19 (1H, s), 7.43 (1H, d), 7.80 (1H, d), 8.57 (1H, d), 8.95 (1H, d), 12.10 (1H, br s). MS (ES): C22H21ClN4O4 requires 440; found 441.1 (M+H+).

1. temperatureThe resulting mixture was heated
2. temperatureat reflux for 5 days
3. temperatureAfter cooling
4. customthe reaction was quenched with water
5. extractionextracted with EtOAc for 3 times
6. washThe combined organic solution was washed with brine
7. dry with materialdried over anhydrous sodium sulfate
8. concentrationThe dried solution was concentrated
9. dissolutionThe residue was dissolved in THF (3 mL)
10. additionSodium hydroxide (40 mg) was added to the mixture
11. additionThen 0.5 M HCl solution was added until pH was about 6
12. concentrationThe solvent was concentrated
13. dissolutionthe residue was dissolved in water
14. customThe precipitate was purified by Mass Directed Auto Prep