4-Bromobenzene-1,2-diamine → 6-Bromo-2-[5-methyl-1-(4-methylbenzyl)-1H-pyrazol-3-yl]-1H-benzimidazole

Participants

Reaction Conditions

Reaction Steps

To a solution of 5-methyl-1-(4-methylbenzyl)-1H-pyrazole-3-carbaldehyde (Step 2, 700 mg, 3.27 mmol) in DMF (25 mL) was added 4-bromo-o-phenylenediamine (1.2 g, 6.53 mmol) followed by sodium bisulfite (679 mg, 6.53 mmol), and the resulting mixture was heated at 110° C. for 5 h. After being cooled to rt, the reaction mixture was diluted with water. The aqueous phase was extracted with ethyl acetate (3×50 mL), and the combined organics were washed with water (1×50 mL) and brine (1×50 mL), dried (Na2SO4), filtered, and concentrated to dryness. The crude material was then purified with an ISCO CombiFlash Companion using gradient elution from 0% to 50% EtOAc in hexanes to afford the title compound as a mixture of regioisomers as a light yellow solid (600 mg, 48%): 1H NMR (300 MHz, DMSO-d6) δ 11.76 (m, 1H), 11.60 (s, 1H), 7.35-7.77 (m, 2H), 7.27-7.30 (m, 1H), 7.13 (d, 2H), 7.04 (d, 2H), 6.69 (s, 1H), 5.36 (s, 2H), 2.27 (s, 3H), 2.24 (s, 3H); ES-MS m/z 381.20, HPLC RT (Method B) 3.20 min.

Provenance & Evidence