反应详情

温度

70 °C

To a round-bottom flask, which was purged and maintained with a nitrogen atmosphere, was added a solution of 4-(1-(5-(5-amino-1,3,4-oxadiazol-2-yl)-4-cyclobutyl-2-ethylbenzoyl)-4-fluoropiperidin-4-yl)benzonitrile (compound 217.3, 200 mg, 0.420 mmol, 1.00 equiv) in methanol (20 mL). Potassium hydroxide (237 mg, 4.22 mmol, 10.0 equiv) was added to the reaction mixture. The resulting solution was stirred for 15 h at 70° C. After cooling to ambient temperature, the organic solvent was removed under reduced pressure. The residue was diluted with 30 mL of H2O, then extracted with 2×50 mL of ethyl acetate. The combined organic layers were washed with 2×50 mL of brine, dried over anhydrous sodium sulfate and concentrated in vacuo. The crude product (50 mg) was purified by Prep-HPLC with the following conditions (1#-Pre-HPLC-001(SHIMADZU)): Column, SunFire Prep C18, 19*150 mm 5 um; mobile phase, water with 0.05% TFA and CH3CN (49.0% CH3CN up to 63.0% in 8 min, up to 100.0% in 1 min, down to 49.0% in 1 min); Detector, Waters 2489 254&220 nm. The fractions containing pure compound were combined and lyophilized to yield 20 mg (10%) of the title compound as a white. m/z (ES+) 488 (M+H)+. 1H-NMR (300 MHz, CD3OD): δ 7.72 (d, 2H), 7.64-7.61 (m, 2H), 7.39-7.25 (m, 2H), 4.85-4.78 (m, 1H), 4.00-3.93 (m, 4H), 3.54-3.49 (m, 2H), 3.28-3.22 (m, 1H), 2.80-2.65 (m, 2H), 2.26-1.84 (m, 10H), 1.45-1.27 (m, 3H).

1. customTo a round-bottom flask, which was purged
2. temperaturemaintained with a nitrogen atmosphere
3. temperatureAfter cooling to ambient temperature
4. customthe organic solvent was removed under reduced pressure
5. additionThe residue was diluted with 30 mL of H2O
6. extractionextracted with 2×50 mL of ethyl acetate
7. washThe combined organic layers were washed with 2×50 mL of brine
8. dry with materialdried over anhydrous sodium sulfate
9. concentrationconcentrated in vacuo
10. customThe crude product (50 mg) was purified by Prep-HPLC with the following conditions (1#-Pre-HPLC-001(SHIMADZU))
11. waitmobile phase, water with 0.05% TFA and CH3CN (49.0% CH3CN up to 63.0% in 8 min
12. waitup to 100.0% in 1 min
13. waitdown to 49.0% in 1 min)
14. additionThe fractions containing pure compound