Oxygen → 6-(4-Fluorophenyl)-2-[5-methyl-1-(4-methylbenzyl)-1H-pyrazol-3-yl]-1H-benzimidazole

Participants

Reaction Steps

To a solution of 6-bromo-2-[5-methyl-1-(4-methylbenzyl)-1H-pyrazol-3-yl]-1-{[2-(trimethylsilyl)ethoxy]methyl}-1H-benzimidazole (Step 1, 150 mg, 0.29 mmol) in dioxane (5 mL) was added (4-fluorophenyl)boronic acid (49 mg, 0.35 mmol) followed by sodium carbonate solution (2.0 M aq., 0.44 mL, 0.88 mmol), and the resultant mixture was freed from oxygen by bubbling a gentle stream of nitrogen through the solution for 10 min. Tetrakis(triphenylphosphine)palladium(0) (34 mg, 0.03 mmol) was then added and the mixture was refluxed for 5 hr. After being cooled to rt, the mixture was diluted with ethyl acetate (50 mL) and washed with water (1×25 mL). The combined organics were dried (Na2SO4), filtered, and concentrated under reduced pressure. The resulting crude material was suspended in dichloromethane (2 mL), TFA (2 mL) was added, and the mixture was stirred at rt for 16 h. The volatiles were removed under reduced pressure and the crude product was purified by HPLC eluting with a gradient from 20% to 80% acetonitrile in water containing 0.1% TFA. The combined fractions were then diluted with ethyl acetate and washed with sat. NaHCO3 solution (1×50 mL), dried (Na2SO4), filtered, and concentrated under reduced pressure to afford the title compound as a light yellow solid (44 mg, 38%): 1H NMR (300 MHz, CD3OD) δ 7.75 (bs, 1H), 7.63-7.69 (m, 3H), 7.52 (dd. 1H), 7.11-7.20 (m, 6H), 6.78 (s, 1H), 5.40 (s, 2H), 2.30 (s, 6H); ES-MS m/z 397.22, HPLC RT (Method B) 3.21 min.

Provenance & Evidence