反应详情

To a suspension of ethyl 5-hydroxypyrazolo[1,5-a]pyrimidine-3-carboxylate (0.541 g, 2.61 mmol) and BOP reagent (1.57 g, 3.56 mmol) in DMF/CH2Cl2 (3 mL/3 mL) at 0° C. was added (R)-5-(5-fluoro-2-methoxyphenyl)pyrrolidin-3-ol hydrochloride (0.588 g, 2.37 mmol) followed by DIEA (1.66 mL, 9.50 mmol). The resulting mixture was warmed to ambient temperature and stirred for 18 hours. The reaction mixture was concentrated under reduced pressure to give the crude material that was diluted again with EtOAc (30 mL). The organic layer was washed with saturated aqueous NaHCO3 followed by brine, dried over MgSO4, filtered, and concentrated under reduced pressure to give the crude material that was purified by silica gel flash column chromatography, eluting with CH2Cl2 to 5% MeOH in CH2Cl2 to afford (R)-ethyl 5-(2-(5-fluoro-2-methoxyphenyl)-4-hydroxypyrrolidin-1-yl)pyrazolo[1,5-a]pyrimidine-3-carboxylate (0.735 g, 1.84 mmol, 77.3% yield). LC/MS (ES+APCI) m/z=401.1 (M+H).

1. concentrationThe reaction mixture was concentrated under reduced pressure
2. customto give the crude material that
3. washThe organic layer was washed with saturated aqueous NaHCO3
4. dry with materialdried over MgSO4
5. filtrationfiltered
6. concentrationconcentrated under reduced pressure
7. customto give the crude material that
8. customwas purified by silica gel flash column chromatography
9. washeluting with CH2Cl2 to 5% MeOH in CH2Cl2