反应详情

温度

120 °C

Into a 10-mL sealed tube, was placed a solution of 4-(1-(3-(2,4-dimethyl-1H-imidazol-5-yl)-4-fluorobenzoyl)piperidin-4-yl)benzonitrile (compound 25.1, 200 mg, 0.50 mmol) in 1,4-dioxane (4 mL). Azetidine hydrochloride (50 mg, 0.53 mmol) and cesium carbonate (500 mg, 1.53 mmol) were added and the mixture was stirred for 48 h at 120° C. behind a blast shield. The mixture was cooled and the solids were removed by filtration. The filtrate was concentrated under reduced pressure and the crude product was purified by Prep-HPLC with the following conditions (1#-Pre-HPLC-001(SHIMADZU)): Column, SunFire Prep C18 OBD Column, 5 um, 19*150 mm; mobile phase, Water with 50 mmol NH4HCO3 and CH3CN (33.0% CH3CN up to 46.0% in 10 min, up to 100.0% in 3 min, down to 33.0% in 1 min); Detector, Waters 2489, 254 & 220 nm. The fractions containing pure compound were combined and lyophilized to yield 59.6 mg (27%) of the title compound as a white solid m/z (ES+) 440 (M+H)+.

1. customInto a 10-mL sealed tube
2. temperatureThe mixture was cooled
3. customthe solids were removed by filtration
4. concentrationThe filtrate was concentrated under reduced pressure
5. customthe crude product was purified by Prep-HPLC with the following conditions (1#-Pre-HPLC-001(SHIMADZU))
6. waitup to 100.0% in 3 min
7. waitdown to 33.0% in 1 min)
8. additionThe fractions containing pure compound