反应详情

To a stirred solution of 5-(4-bromo-2-fluoro-phenylamino)-imidazo[1,5-a]pyrazine-6-carboxylic acid methyl ester (150 mg, 0.41 mmol) and O-(2-vinyloxy-ethyl)hydroxylamine (127 mg, 1.23 mmol, 3.0 eq) in anhydrous THF (7.5 mL) at 0° C. was added lithium hexamethyldisilazide (1M in THF, 1.2 mL, 1.23 mmol, 3.0 eq.), and the reaction, mixture was stirred at room temperature. After 1 h the reaction mixture was quenched with saturated aqueous solution of sodium bicarbonate and diluted with ethyl acetate. The organic layer was isolated and washed with water and brine, dried (Na2SO4), filtered and concentrated in vacuo. The resultant residue was subjected to flash chromatography (Si-PPC, gradient 0 to 5% methanol in dichoromethane) to give an oil. Crystallization from DCM—ether—hexane afforded the desired product as a pale orange solid (160.2 mg, 89.4%). LCMS (method C): RT=2.53 min, [M+H]+=437/439.

1. customthe reaction, mixture
2. customAfter 1 h the reaction mixture was quenched with saturated aqueous solution of sodium bicarbonate
3. additiondiluted with ethyl acetate
4. customThe organic layer was isolated
5. washwashed with water and brine
6. dry with materialdried (Na2SO4)
7. filtrationfiltered
8. concentrationconcentrated in vacuo
9. customto give an oil
10. customCrystallization from DCM—ether—hexane