反应详情

To a solution of 5-(2-fluoro-4-iodo-phenylamino)-imidazo[1,5-a]pyrazine-6-carboxylic acid (64.0 mg, 0.16 mmol) in anhydrous THF (3.6 mL) was added HOBt (56.5 mg, 0.42 mmol, 2.6 eq), DIPEA (0.073 mL, 0.42 mmol, 2.6 mmol), and EDCI (67.8 mg, 0.35 mmol, 2.2 eq), and the reaction mixture was stirred at room temperature under N2 for 2 h. Concentrated aqueous ammonium hydroxide solution (0.50 mL) was added and the reaction mixture was stirred at room temperature for 20 h. The reaction mixture was diluted with ethyl acetate (50 mL) and washed with a saturated aqueous solution of ammonium chloride, water and brine. The organic layer was isolated and dried (Na2SO4), filtered, and concentrated in vacuo. The resultant residue was subjected to flash chromatography (Si-PPC, gradient 0 to 20% methanol in dichloromethane) to give an oil. Crystallization from DCM—ether—hexane afforded the title compound as a beige solid (9.9 mg, 16.0%). 1H NMR (MeOD, 400 MHz) δ ppm 8.74 (s, 1H), 7.86 (s, 1H), 7.79 (s, 1H), 7.62 (dd, J=10.4 Hz, 2.0 Hz, 1H), 7.48 (d, J=8.4 Hz, 1H), 6.59 (t, J=8.4 Hz, 1H); LCMS (method D1): RT=0.84 min, [M+H]+=398.

1. stirringthe reaction mixture was stirred at room temperature for 20 h
2. washwashed with a saturated aqueous solution of ammonium chloride, water and brine
3. customThe organic layer was isolated
4. dry with materialdried (Na2SO4)
5. filtrationfiltered
6. concentrationconcentrated in vacuo
7. customto give an oil
8. customCrystallization from DCM—ether—hexane