反应详情

温度

0 °C

To a stirred solution of [4-(6-amino-5-hydroxy-pyridin-3-yl)-phenyl]-[(2R)-2-pyrrolidin-1-ylmethyl-pyrrolidin-1-yl]-methanone (100 mg, 0.27 mmol) in anhydrous DMF (15 mL) under a N2 atmosphere containing, at 0° C., sodium hydride (60% dispersion in mineral oil, 11 mg, 0.49 mmol) was added. The mixture was allowed to stir at 0° C. for 30 min. 1-(Bromomethyl)-4-fluoro-2-(trifluoromethyl)benzene (0.046 mL, 0.27 mmol) was added. The mixture was stirred at room temperature for 2 hr. The reaction was diluted with EtOAc, and partitioned with H2O. The aqueous layer was extracted with EtOAc (2×25 mL). The organic layers were combined, washed with H2O (1×15 mL), brine (1×15 mL), dried over MgSO4, filtered, concentrated, and purified on a silica gel column to yield {4-[6-amino-5-(4-fluoro-2-trifluoromethyl-benzyloxy)-pyridin-3-yl]-phenyl}-[(2R)-2-pyrrolidin-1-ylmethyl-pyrrolidin-1-yl]-methanone as off-white crystals.

1. stirringThe mixture was stirred at room temperature for 2 hr
2. custompartitioned with H2O
3. extractionThe aqueous layer was extracted with EtOAc (2×25 mL)
4. washwashed with H2O (1×15 mL), brine (1×15 mL)
5. dry with materialdried over MgSO4
6. filtrationfiltered
7. concentrationconcentrated
8. custompurified on a silica gel column