反应详情

温度

110 °C

To a solution of (R)—N-(2-amino-6-(3-(pyrrolidine-1-carbonyl)piperidin-1-yl)pyridine-3-yl)-1-(3-methylisoxazol-5-yl)cyclopropanecarboxamide (94 mg, 0.21 mmol) in isobutanol (2 mL) was added sodium methoxide (25% in methanol, 98 μL, 0.43 mmol) followed by methanol (0.9 mL). The reaction mixture was stirred at 110° C. for 18 h. An additional portion of sodium methoxide (25% in methanol, 98 μL, 0.43 mmol) was added and the reaction mixture was stirred at 110° C. for 3 h. The mixture was concentrated under reduced pressure. The residue was dissolved in dichloromethane, washed with a saturated aqueous solution of sodium bicarbonate, dried over sodium sulfate, filtered and concentrated under reduced pressure. The crude material was purified via HPLC to afford (R)-(1-(2-(1-(3-methylisoxazol-5-yl)cyclopropyl)-3H-imidazo[4,5-b]pyridin-5-yl)piperidin-3-yl)(pyrrolidin-1-yl)methanone. MS (ESI+) (M+H) 421.2; HPLC retention time 2.02 min (Method A).

1. stirringthe reaction mixture was stirred at 110° C. for 3 h
2. concentrationThe mixture was concentrated under reduced pressure
3. dissolutionThe residue was dissolved in dichloromethane
4. washwashed with a saturated aqueous solution of sodium bicarbonate
5. dry with materialdried over sodium sulfate
6. filtrationfiltered
7. concentrationconcentrated under reduced pressure
8. customThe crude material was purified via HPLC