反应详情

5-(methylsulfonyl)-2-(2-((1S,2R)-2-(piperidin-4-yl)cyclopropyl)ethoxy)pyridine (320 mg, 0.98 mmol) was combined with cyanogen bromide (0.395 mL of a 3.0M solution, 1.19 mmol) and sodium bicarbonate (250 mg, 3.0 mmol) at 0° C. in a 10:1 mixture of DCM/water (5 mL), and the resulting slurry stirred for 30 min and warmed to ambient temperature. After 3 hr, HPLC/MS indicated no starting material. The reaction mixture was diluted with dichloromethane (10 mL), water (3 mL) and the layers separated. The organic layer was dried over magnesium sulfate, filtered, concentrated in vacuo and purified by flash chromatography (10-40% acetone/hexanes, 25S+ column) to afford a white film (not weighed). The material was dissolved in 3 mL of methanol and to this solution was added hydroxylamine (82 mg, 1.19 mmol) and triethylamine (0.2 mL, 1.48 mmol). The mixture was then heated to reflux for 2 hrs and then cooled to ambient temperature. The mixture was concentrated under reduced pressure and the residue was purified by flash chromatography (3.5% methanol/95.5% dichloromethane/1% NH4OH, 25S+ column) to afford title compound as a white foam. HPLC/MS; 0.99 min, 383 (M+H)+.

1. customat 0° C.
2. waitAfter 3 hr
3. customthe layers separated
4. dry with materialThe organic layer was dried over magnesium sulfate
5. filtrationfiltered
6. concentrationconcentrated in vacuo
7. custompurified by flash chromatography (10-40% acetone/hexanes, 25S+ column)
8. customto afford a white film (not
9. temperatureThe mixture was then heated
10. temperatureto reflux for 2 hrs
11. temperaturecooled to ambient temperature
12. concentrationThe mixture was concentrated under reduced pressure
13. customthe residue was purified by flash chromatography (3.5% methanol/95.5% dichloromethane/1% NH4OH, 25S+ column)