反应详情

温度

80 °C

To a solution of (R)-(1-(5,6-diaminopyridin-2-yl)piperidin-3-yl)(pyrrolidin-1-yl)methanone dihydrochloride (125 mg, 0.3 mmol) in anhydrous N,N-dimethylformamide (2.5 mL) was added 3-(methylsulfonyl)benzaldehyde (76 mg, 0.4 mmol). The solution was stirred at 80° C. for 1 h. Sulfur was added (25 mg, 0.8 mmol) followed by triethylamine (140 μL, 1.0 mmol). The mixture was stirred at 85° C. for 24 h followed by stirring at room temperature for another 24 h. The mixture was concentrated under reduced pressure and the residue was partitioned between dichloromethane and water. The aqueous layer was extracted with dichloromethane and the combined extracts were dried over magnesium sulfate, filtered and concentrated under reduced pressure. The residue was purified via flash chromatography (20-100% ethyl acetate in heptanes gradient followed by 0-10% methanol in dichloromethane). The residue was repurified via flash chromatography (0-10% methanol in dichloromethane) to afford a yellow solid that was stirred in acetonitrile (3 mL) at 40° C. for 2.5 h. The solid was filtered, washed with cold acetonitrile and dried under high vacuum at 40° C. to afford the title compound. 1H NMR (500 MHz, CD3OD) δ 1.60-1.74 (m, 1H) 1.77-1.89 (m, 2H) 1.89-2.11 (m, 4H) 2.81 (br s, 1H) 2.97-3.09 (m, 2H) 3.17-3.26 (m, 3H) 3.41-3.52 (m, 2H) 3.52-3.63 (m, 1H) 3.74 (br s, 1H) 4.37 (br s, 1H) 4.64 (d, 1H) 6.91 (br s, 1H) 7.74-7.89 (m, 2H) 8.05 (d, 1H) 8.35 (br s, 1H) 8.65 (br s, 1H).

1. stirringThe mixture was stirred at 85° C. for 24 h
2. stirringby stirring at room temperature for another 24 h
3. concentrationThe mixture was concentrated under reduced pressure
4. customthe residue was partitioned between dichloromethane and water
5. extractionThe aqueous layer was extracted with dichloromethane
6. dry with materialthe combined extracts were dried over magnesium sulfate
7. filtrationfiltered
8. concentrationconcentrated under reduced pressure
9. customThe residue was purified via flash chromatography (20-100% ethyl acetate in heptanes gradient followed by 0-10% methanol in dichloromethane)
10. customThe residue was repurified via flash chromatography (0-10% methanol in dichloromethane)
11. customto afford a yellow solid
12. filtrationThe solid was filtered
13. washwashed with cold acetonitrile
14. customdried under high vacuum at 40° C.