反应详情

温度

140 °C

A mixture of 4-amino-6-[(S)-1-(7-bromo-6-fluoro-1-methyl-1H-benzoimidazol-2-yl)ethylamino]-pyrimidine-5-carbonitrile, (0.10 g, 0.26 mmol), 3-pyridylboronic acid (0.041 g, 0.33 mmol), tetrakis(triphenylphosphine)palladium(0) (0.015 g, 0.013 mmol) and caesium carbonate (0.17 g, 0.51 mmol) in dioxane (3 mL) and water (1.5 mL) was placed in a sealed tube and degassed with nitrogen for 5 min, then heated for 30 minutes at 140° C. by microwave irradiation. The resulting mixture was loaded onto an Isolute® SCX-2 cartridge then washed with MeOH and the product eluted with 2M NH3/MeOH and concentrated in vacuo. The resulting residue was purified by chromatography (SiO2, 0-10% (2M ammonia in methanol) in DCM) then by preparative HPLC (Phenomenex Gemini 5 μm C18 on a 78 min gradient 20-98% 0.1% HCO2H in acetonitrile/water) to give 425 as a white solid (0.066 g, 66%). LCMS (Method K): RT 2.50 min [M+H]+ 389.1. 1H NMR (DMSO-d6, 400 MHz): δ 8.72-8.64 (2H, m), 8.22-8.03 (1H, m), 7.97-7.90 (1H, m), 7.75-7.65 (2H, m), 7.57-7.53 (1H, m), 7.30 (2H, s), 7.21-7.17 (1H, m), 5.63 (1H, m), 3.19-3.17 (3H, m), 1.58 (3H, d, J=6.72 Hz)

1. customwas placed in a sealed tube
2. customdegassed with nitrogen for 5 min
3. washthen washed with MeOH
4. washthe product eluted with 2M NH3/MeOH
5. concentrationconcentrated in vacuo
6. customThe resulting residue was purified by chromatography (SiO2, 0-10% (2M ammonia in methanol) in DCM)