反应详情

To a stirred solution of (S)-5-isopropyl-1-(3-(4-(1-((2-(trimethylsilyl)ethoxy)methyl)-1H-1,2,4-triazol-3-yl)phenyl)pyrazolo[1,5-a]pyrimidin-5-yl)imidazolidin-2-one (Example 25, Step 4; 80 mg, 0.15 mmol) in DMF (1 mL) was added NaH (60% dispersion in mineral oil, 12 mg, 0.31 mmol) at 0° C. under N2. After stirring at ambient temperature for 30 minutes, a solution of tert-butyl 4-(bromomethyl)piperidine-1-carboxylate (77 mg, 0.28 mmol) in DMF (0.5 mL) was added dropwise. The reaction mixture was heated at 80° C. for 1 hour. After cooling, the reaction mixture was partitioned between EtOAc and water. The aqueous layer was extracted with EtOAc. The combined organic layers were washed with brine, dried and concentrated. The residue was purified by column chromatography (hexane:EtOAc, 1:4) to give (S)-tert-butyl 4-((4-isopropyl-2-oxo-3-(3-(4-(1-((2-(trimethylsilyl)ethoxy)methyl)-1H-1,2,4-triazol-3-yl)phenyl)pyrazolo[1,5-a]pyrimidin-5-yl)imidazolidin-1-yl)methyl)piperidine-1-carboxylate (99 mg, 90%).

1. temperatureThe reaction mixture was heated at 80° C. for 1 hour
2. temperatureAfter cooling
3. customthe reaction mixture was partitioned between EtOAc and water
4. extractionThe aqueous layer was extracted with EtOAc
5. washThe combined organic layers were washed with brine
6. customdried
7. concentrationconcentrated
8. customThe residue was purified by column chromatography (hexane:EtOAc, 1:4)