反应详情

温度

60 °C

To a mixture of 2-[(3S,4R)-3-amino-4-methylpyrrolidin-1-yl]-6-methyl-N-(1H-pyrazol-3-yl)pyrimidin-4-amine (20 mg) in CHCl3 (10 ml) was added 4-nitrophenyl (2S)-1,1,1-trifluoropropan-2-yl carbonate (41 mg) prepared in Step 1 of Example 1 and DIEA (19 mg) at room temperature. After 4-hour stirring at 60° C., the resulting mixture was cooled to room temperature and concentrated. The residue was diluted with MeOH (5 mL). To the resulting mixture was added potassium carbonate (100 mg) at 0° C. and stirred at 0° C. for 30 min. The mixture was poured into saturated aqueous solution of NH4Cl and extracted with CHCl3. The extract was washed with brine, dried over MgSO4 and concentrated. The residue was purified with silica gel column chromatography (eluent: CHCl3/MeOH=99/1˜80/20) to give (2S)-1,1,1-trifluoropropan-2-yl{(3R,4R)-4-methyl-1-[4-methyl-6-(1H-pyrazol-3-ylamino)pyrimidin-2-yl]pyrrolidin-3-yl}carbamate as a pale yellow foam.

1. temperaturethe resulting mixture was cooled to room temperature
2. concentrationconcentrated
3. additionThe residue was diluted with MeOH (5 mL)
4. additionTo the resulting mixture was added potassium carbonate (100 mg) at 0° C.
5. stirringstirred at 0° C. for 30 min
6. additionThe mixture was poured into saturated aqueous solution of NH4Cl
7. extractionextracted with CHCl3
8. washThe extract was washed with brine
9. dry with materialdried over MgSO4
10. concentrationconcentrated
11. customThe residue was purified with silica gel column chromatography (eluent: CHCl3/MeOH=99/1˜80/20)