反应详情

温度

140 °C

A mixture of 4-amino-6-[(S)-1-(7-bromo-1-cyclopropyl-6-fluoro-1H-benzoimidazol-2-yl)ethylamino]pyrimidine-5-carbonitrile (68 mg, 0.16 mmol), phenylboronic acid (26 mg, 0.21 mmol), tetrakis(triphenylphosphine)palladium (19 mg, 10 mol %) and caesium carbonate (106 mg, 0.33 mol) in dioxane (3 mL) and H2O (1.5 mL) was purged with argon gas then heated at 140° C., for 30 min, by microwave irradiation. After cooling to RT, the reaction mixture was diluted with MeOH and loaded into an Isolute® SCX-2 cartridge. The cartridge was washed with MeOH followed by 2M NH3/MeOH. The basic fractions were combined, concentrated in vacuo and the resulting residue purified by column chromatography (Si—PCC, gradient 0-100% EtOAc in DCM) followed by recrystallisation from EtOAc/cyclohexane to afford 415 as a white solid (10 mg, 15%). LCMS (Method K): RT 4.08 min [M+H]+ 414.08. 1H NMR (CDCl3 400 MHz): δ 8.17 (1H, s), 7.65 (1H, dd, J=8.89, 4.63 Hz), 7.43-7.42 (5H, m), 7.09 (1H, dd, J=10.20, 8.76 Hz), 6.35 (1H, d, J=7.83 Hz), 5.96 (1H, m), 5.32 (2H, s), 2.89-2.83 (1H, m), 1.69 (3H, d, J=6.74 Hz), 0.79 (1H, m), 0.61 (1H, m), 0.47 (1H, m), 0.23 (1H, m)

1. customwas purged with argon gas
2. temperatureAfter cooling to RT
3. additionthe reaction mixture was diluted with MeOH
4. washThe cartridge was washed with MeOH
5. concentrationconcentrated in vacuo
6. customthe resulting residue purified by column chromatography (Si—PCC, gradient 0-100% EtOAc in DCM)
7. customfollowed by recrystallisation from EtOAc/cyclohexane