反应详情

A mixture of (R)-5-(2-(2,5-difluorophenyl)pyrrolidin-1-yl)pyrazolo[1,5-a]pyrimidine-3-carboxylic acid (Preparation C, 400 mg, 1.16 mmol), HATU (486 mg, 1.28 mmol), and (S)-3-aminopropane-1,2-diol (318 mg, 3.49 mmol) in dry DMF (3.0 mL) was stirred for 1-2 minutes at ambient temperature. Diisopropylethylamine (DIEA) (0.62 mL, 3.49 mmol) was added and the reaction was flushed with N2, sealed and stirred at ambient temperature for 18 hours. The reaction mixture was added to H2O (15 mL), mixed and extracted with EtOAc. The combined EtOAc extracts were washed with H2O, saturated NaHCO3 and dried over MgSO4/activated carbon. The solution was eluted through a SiO2 column eluting first with EtOAc then 10% MeOH/EtOAc. The 10% MeOH/EtOAc pool was concentrated and the residual, colorless glass was dissolved in a minimal amount of CH2Cl2. Hexane was added and the resulting white suspension was sonicated and concentrated to give the title product as a white solid (205 mg, 42%). MS (apci) m/z=418.1 (M+H).

1. customthe reaction was flushed with N2
2. customsealed
3. stirringstirred at ambient temperature for 18 hours
4. additionThe reaction mixture was added to H2O (15 mL)
5. additionmixed
6. extractionextracted with EtOAc
7. washThe combined EtOAc extracts were washed with H2O, saturated NaHCO3
8. dry with materialdried over MgSO4/activated carbon
9. washThe solution was eluted through a SiO2 column
10. washeluting first with EtOAc
11. concentrationThe 10% MeOH/EtOAc pool was concentrated
12. dissolutionthe residual, colorless glass was dissolved in a minimal amount of CH2Cl2
13. additionHexane was added
14. customthe resulting white suspension was sonicated
15. concentrationconcentrated