反应详情

温度

140 °C

A mixture of [(S)-1-(7-bromo-6-fluoro-1-methyl-1H-benzoimidazol-2-yl)ethyl]-(9H-purin-6-yl)amine, (0.10 g, 0.26 mmol), 4-pyridylboronic acid (0.041 g, 0.33 mmol), tetrakis(triphenylphosphine)palladium(0) (0.015 g, 0.01 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 minutes, then heated for 45 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 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 433 as a white solid (0.019 g, 20%). LCMS (Method K): RT 2.10 min [M+H]+ 389.1. 1H NMR (DMSO-d6, 400 MHz): δ 12.70 (1H, s), 8.70 (2H, s), 8.25-8.13 (2H, m), 7.95 (1H, d), 7.71 (1H, dd, J=8.80, 4.80 Hz), 7.53 (2H, d, J=17.59 Hz), 7.17 (1H, dd, J=10.45, 8.79 Hz), 5.85-5.73 (1H, m), 3.30 (3H, s), 1.66 (3H, d, J=6.75 Hz). Signals split due to presence of tautomers

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