反应详情

温度

130 °C

8-Oxo-5,6,7,8-tetrahydroimidazo[1,2-a]pyrazine hydrochloride (87 mg, 0.53 mmol), prepared as described in Example 25, was reacted with 5′-bromo-4,2′-difluorobiphenyl-2-carbonitrile (prepared as described in WO 02/074773, 204 mg, 1.3 mol eq) in DMA (2 ml) in the presence of potassium acetate (280 mg, 1.5 mol eq), palladium acetate (6 mg, 5 mol %) and triphenylphosphine (7 mg, 5 mol %). After bubbling nitrogen through the reaction mixture for 10 min, the temperature was raised to 130° C. and heating continued for 3 h. After cooling, the crude reaction mixture was poured onto a column of silica and purified using 0-5% methanol in dichloromethane as eluent. Recrystallization from ethyl acetate/dichloromethane gave 4,2′-difluoro-5′-(8-oxo-7,8-dihydroimidazo[1,2-a]pyrazin-3-yl)biphenyl-2-carbonitrile (126 mg): δH (400 MHz, DMSO) 3.54-3.58 (2H, m), 4.28-4.32 (2H, m), 7.39 (1H, s), 7.54-7.59 (1H, m), 7.71-7.78 (4H, m), 8.05-8.08 (1H, m), 8.18 (1H, br s); m/z (ES+) 351 [M+H]+.

1. customAfter bubbling nitrogen through the reaction mixture for 10 min
2. temperatureheating
3. temperatureAfter cooling
4. customthe crude reaction mixture
5. additionwas poured onto a column of silica
6. custompurified
7. customRecrystallization from ethyl acetate/dichloromethane