反应详情

To a microwave vial with stir bar was added 4-(4-bromo-2-cyclopropyl-1-((2-(trimethylsilyl)ethoxy) methyl)-1H-imidazol-5-yl)-2-chloropyrimidine (I-1a, step 5, 0.55 g, 1.3 mmol), 2-fluoro-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)aniline (0.61 g, 2.6 mmol), 2.0 M aqueous sodium carbonate solution (3.2 mL, 6.4 mmol) and DME (6.4 mL). The resulting mixture was sparged with nitrogen followed by the addition of PdCl2(dppf).DCM adduct (0.052 g, 0.06 mmol). The reaction was sealed and irradiated in microwave reactor for 20 minutes at 120° C. The reaction mixture was diluted with a saturated aqueous NH4Cl solution and extracted with EtOAc. The organic phase was washed with water, brine, dried (Na2SO4), filtered, concentrated, and adsorbed onto silica gel. Purification by flash chromatography (SiO2, 0-100% EtOAc in heptane) yielded 3-(5-(2-chloropyrimidin-4-yl)-2-cyclopropyl-1-((2-(trimethylsilyl)ethoxy) methyl)-1H-imidazol-4-yl)-2-fluoroaniline (223 mg, 0.48 mmol, 38%) as a viscous yellow oil: LCMS (m/z) 460.1 (MH+), tR=0.95 minute.

1. customThe resulting mixture was sparged with nitrogen
2. additionfollowed by the addition of PdCl2(dppf)
3. customThe reaction was sealed
4. customirradiated in microwave reactor for 20 minutes at 120° C
5. extractionextracted with EtOAc
6. washThe organic phase was washed with water, brine
7. dry with materialdried (Na2SO4)
8. filtrationfiltered
9. concentrationconcentrated
10. customPurification by flash chromatography (SiO2, 0-100% EtOAc in heptane)