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), phenylboronic 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 and washed with MeOH then the product eluted with 2M NH3/MeOH. then concentrated in vacuo. The resulting residue was purified by chromatography (SiO2, 0-7% (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). The relevant fractions were concentrated to approximately ⅓ volume and partitioned between DCM (3×) and saturated aqueous NaHCO3. The combined DCM extracts were dried (Na2SO4) and concentrated in vacuo to give 424 as a white solid (0.058 g, 58%). LCMS (Method K): RT 3.55 min [M+H]+ 388.0. 1H NMR (DMSO-d6, 400 MHz): δ 8.03 (1H, s), 7.66-7.62 (2H, m), 7.52-7.41 (5H, m), 7.30 (2H, s), 7.13 (1H, m), 5.61 (1H, m), 3.15 (3H, s), 1.57 (3H, d, J=6.72 Hz)

1. customwas placed in a sealed tube
2. customdegassed with nitrogen for 5 min
3. washwashed with MeOH
4. washthe product eluted with 2M NH3/MeOH
5. concentrationthen concentrated in vacuo
6. customThe resulting residue was purified by chromatography (SiO2, 0-7% (2M ammonia in methanol) in DCM)
7. customC18 on a 78 min gradient 20-98% 0.1% HCO2H in acetonitrile/water
8. concentrationThe relevant fractions were concentrated to approximately ⅓ volume
9. custompartitioned between DCM (3×) and saturated aqueous NaHCO3
10. dry with materialThe combined DCM extracts were dried (Na2SO4)
11. concentrationconcentrated in vacuo