Cesium carbonate → 4-{3-[1-(2,2-dimethylpropyl)-4-fluoro-3-methyl-2-oxo-2,3-dihydro-1H-benzimidazol-5-yl]phenoxy}benzonitrile

Participants

Reaction Steps

A solution of 1-(2,2-dimethylpropyl)-4-fluoro-5-(3-hydroxyphenyl)-3-methyl-1,3-dihydro-2H-benzimidazol-2-one (7-15, 55 mg, 0.17 mmol) in NMP (1 ml) was sequentially charged with 4-Bromobenzonitrile (61.0 mg, 0.34 mmol, 2.0 eq), Cesium carbonate (109 mg, 0.34 mmol, 2.0 eq) and Copper(I) iodide (31.9 mg, 0.17 mmol, 1.0 eq). The resulting mixture was irradiated in a microwave at 195 deg C. for 2 h. LC/MS analysis showed only partial conversion, therefore additional amounts of 4-Bromobenzonitrile (61.0 mg, 0.34 mmol, 2.0 eq) and Cu(I)I (31.9 mg, 0.17 mmol, 1.0 eq) were added and the reaction was irradiated again at 195 deg C. for 1 h. The completed reaction was filtered and the filtrate purified via reverse-phase HPLC (Acetonitrile/Water gradient with 0.1% TFA present) to afford the title compound, 4-{3-[1-(2,2-dimethylpropyl)-4-fluoro-3-methyl-2-oxo-2,3-dihydro-1H-benzimidazol-5-yl]phenoxy}benzonitrile (9-1), as a tan solid-oil. 1H NMR (400 MHz, CDCl3) δ 7.62 (d, 2H, J=8.9 Hz), 7.50-7.46 (m, 1H), 7.39 (m, 1H), 7.25 (s, 1H), 7.09-7.04 (m, 4H), 6.87 (d, 1H, J=8.2 Hz), 3.67 (s, 2H), 3.64 (s, 3H), 1.05 (s, 9H). LRMS m/z: Calc'd for C26H24FN3O2(M+H) 430.2, found 430.5.

Provenance & Evidence