反应详情

4-Cyano-2-{5-[4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-phenyl]-1H-imidazol-2-yl}-pyrrolidine-1-carboxylic acid tert-butyl ester (0.990 g, 2.13 mmol), (1-{6-[5-(6-Bromo-naphthalen-2-yl)-1H-imidazol-2-yl]-5-aza-spiro[2.4]heptane-5-carbonyl}-2-methyl-propyl)-carbamic acid methyl ester (1.007 g, 1.92 mmol), Pd(PPh3)4 (222 mg, 0.192 mmol) and K2CO3 (2.0 M in H2O, 2.1 mL, 4.2 mmol) were combined in 1,2-dimethoxymethane. The mixture was degassed for 10 min with bubbling N2 then heated to reflux for 4 h then cooled. The reaction mixture was diluted with EtOAc and washed with saturated aqueous NaHCO3 and brine before being dried over MgSO4, filtered and concentrated. The crude residue was purified by silica column chromatography (EtOAc, then 2% MeOH/DCM, then 4% MeOH/DCM) to provide the title compound (1.028 g, 68%).

1. customThe mixture was degassed for 10 min with bubbling N2
2. temperaturethen heated
3. temperatureto reflux for 4 h
4. temperaturethen cooled
5. additionThe reaction mixture was diluted with EtOAc
6. washwashed with saturated aqueous NaHCO3 and brine
7. dry with materialbefore being dried over MgSO4
8. filtrationfiltered
9. concentrationconcentrated
10. customThe crude residue was purified by silica column chromatography (EtOAc