反应详情

温度

150 °C

A mixture of 4-amino-6-[(S)-1-(7-bromo-1-cyclopropyl-6-fluoro-1H-benzoimidazol-2-yl)ethylamino]pyrimidine-5-carbonitrile (70 mg, 0.17 mmol), 2-(tributylstannyl)pyridine (0.06 mL, 0.19 mmol), tetrakis(triphenylphosphine)palladium (19 mg, 10 mol %) and copper(I)-thiophene-2-carboxylate (6 mg, 20 mol %) in dioxane (1 mL) was purged with argon gas then heated at 150° C., for 20 min, in a microwave reactor (Biotage). After cooling to RT, the reaction mixture was diluted with MeOH and loaded onto 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 0-10% MeOH in EtOAc) to afford 442 as a pale yellow solid (17 mg, 24%). LCMS (Method K): RT 3.05 min [M+H]+ 415.07. 1H NMR (DMSO-d6, 400 MHz): δ 8.72 (1H, ddd, J=4.87, 1.81, 0.94 Hz), 8.02 (1H, s), 7.94 (1H, td, J=7.71, 1.84 Hz), 7.73-7.66 (3H, m), 7.45 (1H, ddd, J=7.59, 4.87, 1.16 Hz), 7.30 (2H, s), 7.16 (1H, dd, J=10.65, 8.75 Hz), 5.84-5.75 (1H, m), 3.02-2.95 (1H, m), 1.61 (3H, d, J=6.76 Hz), 1.25-1.20 (1H, m), 0.79-0.69 (1H, m), 0.52-0.43 (1H, m), 0.41-0.28 (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 0-10% MeOH in EtOAc)