Potassium Carbonate → 3-{1-(4-Bromobenzyl)-6-[(1-methyl-1H-pyrazol-3-yl)methoxy]-1H-benzimidazol-2-yl}-2,2-dimethylpropanoic acid

Beteiligte Stoffe

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Reaktionsschritte

A mixture of ethyl 3-(1-(4-bromobenzyl)-6-hydroxy-1H-benzo[d]imidazol-2-yl)-2,2-dimethylpropanoate (322 mg, 0.75 mmol), 3-(chloromethyl)-1-methyl-1H-pyrazole (97.5 mg, 0.75 mmol) and K2CO3 (310 mg, 2.25 mmol) in DMF (20 mL) was stirred at 50° Celsius for 18 h. The resulting residue was dissolved in THF (9 mL), MeOH (9 mL) and NaOH (2 mL, 5%). The mixture was stirred at 40° Celsius. After 16 h the reaction was concentrated to dryness and the residue was dissolved in water (30 mL), washed with EtOAc (20 mL). The aqueous layer was separated and acidified to pH ˜6 with HCl (6 N) then extracted with DCM (2×30 mL). The combined organic layers were dried over Na2SO4, filtered, concentrated to dryness and purified by reverse phase HPLC to give the title compound (63 mg, 19%). MS (ESI): mass calcd. for C24H25BrN4O3, 496.11; m/z found, 497.1 [M+H]+. 1H NMR (300 MHz, CD3OD) δ 7.84 (d, J=2.4, 1H), 7.76 (d, J=9.0, 1H), 7.54 (d, J=8.5, 2H), 7.32 (dd, J=9.0, 2.3, 1H), 7.27 (d, J=2.1, 1H), 7.16 (d, J=8.4, 2H), 6.49 (d, J=2.4, 1H), 5.83 (s, 2H), 5.21 (s, 2H), 3.98 (s, 3H), 3.51 (s, 2H), 1.41 (s, 6H).

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