反应详情

温度

40 °C

1-(3-Methylisoxazol-5-yl)cyclopropanecarboxylic acid (40 mg, 0.24 mmol), (R)-(1-(5,6-diaminopyridin-2-yl)piperidin-3-yl)(pyrrolidin-1-yl)methanone dihydrochloride (Intermediate 1) (86 mg, 0.24 mmol), and diisopropylethylamine (200 μL, 1.2 mmol) were combined and dissolved in N,N-dimethylformamide (1.25 mL). O-Benzotriazole-N,N,N′,N′,-tetramethyluronium hexafluorophosphate (HBTU) (109 mg, 0.287 mmol) was added and the reaction mixture was stirred at 40° C. for 18 h. The solvent was removed under reduced pressure and the residue was dissolved in dichloromethane. A saturated aqueous solution of sodium bicarbonate was added. The organics were collected and the aqueous layer was extracted with dichloromethane. The combined organics were washed with brine, dried over sodium sulfate, filtered and concentrated under reduced pressure. The residue was purified via flash chromatography (0-12% methanol in dichloromethane) to afford (R)—N-(2-amino-6-(3-(pyrrolidine-1-carbonyl)piperidin-1-yl)pyridine-3-yl)-1-(3-methylisoxazol-5-yl)cyclopropanecarboxamide (56 mg, 53%). MS (ES+) (M+H) 439.2; LCMS retention time 1.94 min (Method L).

1. customThe solvent was removed under reduced pressure
2. dissolutionthe residue was dissolved in dichloromethane
3. additionA saturated aqueous solution of sodium bicarbonate was added
4. customThe organics were collected
5. extractionthe aqueous layer was extracted with dichloromethane
6. washThe combined organics were washed with brine
7. dry with materialdried over sodium sulfate
8. filtrationfiltered
9. concentrationconcentrated under reduced pressure
10. customThe residue was purified via flash chromatography (0-12% methanol in dichloromethane)