反应详情

温度

0 °C

To the solution of (4S)-7-(3,5-dimethylisoxazol-4-yl)-4-pyridin-2-yl-4,5-dihydroimidazo[1,5,4-de][1,4]benzoxazine-2-carbaldehyde (8 mg, 0.02 mmol) in tetrahydrofuran (1 mL) at 0° C., 3.0 M methylmagnesium chloride in THF (0.01 mL, 0.04 mmol) [Aldrich, cat. #189901] was added dropwise. After continued stirring for 30 min at 0° C., the reaction was quenched by adding saturated aqueous ammonium chloride (0.5 mL) dropwise. The resulting mixture was diluted with ethyl acetate/brine (3:1), and the organic layer was separated. The aqueous layer was extracted with ethyl acetate. The combined organic layers were dried over sodium sulfate, filtered, and concentrated under vacuum. Purification by preparative LCMS (XBridge C18 column, eluting with a gradient of acetonitrile/water containing 0.1% ammonium hydroxide, at flow rate of 60 mL/min) afforded the desired product as a mixture of diastereomers (4 mg, 50%). LCMS for C21H21O3N4 (M+H)+: calculated m/z=377.2. found 377.1.

1. customthe reaction was quenched
2. additionby adding saturated aqueous ammonium chloride (0.5 mL) dropwise
3. additionThe resulting mixture was diluted with ethyl acetate/brine (3:1)
4. customthe organic layer was separated
5. extractionThe aqueous layer was extracted with ethyl acetate
6. dry with materialThe combined organic layers were dried over sodium sulfate
7. filtrationfiltered
8. concentrationconcentrated under vacuum
9. customPurification by preparative LCMS (XBridge C18 column
10. washeluting with a gradient of acetonitrile/water containing 0.1% ammonium hydroxide, at flow rate of 60 mL/min)