反应详情

温度

90 °C

To a solution of ethyl 3-[7-(5-{5-chloro-6-[(1-methylethyl)oxy]-3-pyridinyl}-1,2,4-oxadiazol-3-yl)-6-fluoro-1-methyl-1H-indol-3-yl]propanoate (D150) (270 mg) in isopropanol (7 mL) and water (7 mL) was added NaOH (5.6 mL, 0.5 M aq) at room temperature. The reaction suspension was stirred at 90° C. for 2 hours until the solution turned clear. Isopropanol was removed in vacuo and water (8 mL) was added to the residue. The aqueous solution was acidified to pH=1 and extracted with ethyl acetate (3×10 mL). The combined organic phase was dried over sodium sulphate. The organic solution was concentrated and the residue was purified by MDAP to afford 3-[7-(5-{5-chloro-6-[(1-methylethyl)oxy]-3-pyridinyl}-1,2,4-oxadiazol-3-yl)-6-fluoro-1-methyl-1H-indol-3-yl]propanoic acid (E108) (72 mg) as a white solid. δH (DMSO-d6, 400 MHz): 1.32 (6H, d), 2.53 (2H, t), 2.88 (2H, t), 3.28 (3H, s), 5.39 (1H, m), 7.02 (1H, m), 7.11 (1H, s), 7.75 (1H, m), 8.53 (1H, d), 8.90 (1H, d), 12.07 (1H, s). MS (ES): C22H20ClFN4O4 requires 458; found 459.2 (M+H+).

1. customIsopropanol was removed in vacuo and water (8 mL)
2. additionwas added to the residue
3. extractionextracted with ethyl acetate (3×10 mL)
4. dry with materialThe combined organic phase was dried over sodium sulphate
5. concentrationThe organic solution was concentrated
6. customthe residue was purified by MDAP