反应详情

温度

95 °C

To a suspension of 3-(2-fluoro-4-iodo-phenylamino)-5-formylaminomethyl-pyrazine-2-carboxylic acid methyl ester (480 mg, 1.12 mmol) in toluene (18 mL) was added phosphorous oxychloride (0.42 mL, 4.4 mmol, 4.0 eq.), and the reaction mixture was heated at 95° C. for 1 hour. The reaction mixture was cooled to RT and then quenched with a saturated aqueous solution of sodium bicarbonate (2 mL). The resultant residue was dissolved in ethyl acetate and washed with water and brine. The organic phase was isolated, dried (Na2SO4), filtered and concentrated in vacuo. The resultant residue was subjected to flash chromatography (Si-PPC, gradient 0% to 20%, methanol in ethyl acetate) to give a yellow oil. Crystallization from dichloromethane—ether—hexane afforded the desired product as a yellow solid (190 mg, 41.3%). LCMS (method C): RT=2.45 min, [M+H]+=413.

1. temperatureThe reaction mixture was cooled to RT
2. customquenched with a saturated aqueous solution of sodium bicarbonate (2 mL)
3. dissolutionThe resultant residue was dissolved in ethyl acetate
4. washwashed with water and brine
5. customThe organic phase was isolated
6. dry with materialdried (Na2SO4)
7. filtrationfiltered
8. concentrationconcentrated in vacuo
9. customto give a yellow oil
10. customCrystallization from dichloromethane—ether—hexane