反应详情

温度

0 °C

A mixture of 1-[3-(4-Chloro-2-methyl-2H-pyrazol-3-yl)-4-methoxy-phenyl]-3-(2,4-difluoro-phenyl)urea (Compound 77, example 1.61) (0.270 g, 0.69 mmol) in anhydrous 1,2-dichloroethane (10 mL) was cooled to 0° C. on an ice bath and stirred for 10 minutes. Anhydrous aluminium 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. Organic layer was separated, dried over anhydrous Na2SO4, filtered and concentrated to give the crude product that was further purified via HPLC. The corresponding fractions were collected and lyophilized to afford Compound 120 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).

1. stirringthe reaction mixture stirred at 0° C. for 20 minutes
2. custommoved to an oil bath
3. stirringstirred at 80° C. for 1 hour
4. washwashed with potassium sodium tartrate (10%) twice
5. customOrganic layer was separated
6. dry with materialdried over anhydrous Na2SO4
7. filtrationfiltered
8. concentrationconcentrated
9. customto give the crude product that
10. customwas further purified via HPLC
11. customThe corresponding fractions were collected