Ethyl Acetate → 1-[3-(4-Chloro-2-methyl-2H-pyrazol-3-yl)4-hydroxy-phenyl]-3-(2,4-difluoro-phenyl)-urea

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Reaction Conditions

Reaction Steps

A mixture of 1-[3-(4-chloro-2-methyl-2H-pyrazol-3-yl)-4-methoxy-phenyl]-3-(2,4-difluoro-phenyl)urea (0.270 g, 0.69 mmol) in anhydrous 1,2-dichloroethane (10 mL) was cooled to 0° C. in an ice bath and stirred for 10 minutes. Anhydrous aluminum chloride (0.368 g, 2.76 mmol) was added and the reaction mixture stirred at 0° C. for 20 minutes, then moved to an oil bath and stirred at 80° C. for 1 hour. Ethyl acetate was added and washed with potassium sodium tartrate (10%) twice. The organic layer was separated, dried over anhydrous Na2SO4, filtered and concentrated to give a crude product that was subjected to purification on HPLC. The proper fractions were collected and lyophilized to afford 1-[3-(4-chloro-2-methyl-2H-pyrazol-3-yl)-4-hydroxy-phenyl]-3-(2,4-difluoro-phenyl)-urea as a white solid in 75.0% yield. LCMS m/z (%)=379 (M+H35Cl, 100), 381 (M+H37Cl, 40). 1H NMR (400 MHz, DMSO-d6) δ 9.81 (s, 1H), 8.92 (s, 1H), 8.45 (s, 1H), 8.12-8.06 (m, 1H), 7.63 (s, 1H), 7.40-7.31 (m, 3H), 7.09-7.04 (m, 1H), 6.99 (d, J1=8.72 Hz, 1H), 3.69 (s, 3H).

Provenance & Evidence