反应详情

温度

90 °C

N-(4-((2-Chloropyridin-4-yl)oxy)-2,5-difluorophenyl)-1-(4-fluorophenyl)-4-isopropoxy-2-oxo-1,2-dihydropyridine-3-carboxamide (180 mg, 0.340 mmol), Cs2CO3 (400 mg, 1.228 mmol), propionamide (200 mg, 2.74 mmol) and Xantphos (20 mg, 0.035 mmol) were combined in dioxane (10 mL), sparged with argon under sonication, treated with Pd2(dba)3 (15 mg, 0.016 mmol) and heated to 90° C. overnight. The solids were collected by filtration and washed with DCM and MeCN. The filtrate was evaporated and the residue purified by silica gel chromatography (0-100% EtOAc/DCM) to provide N-(2,5-difluoro-4-((2-propionamidopyridin-4-yl)oxy)phenyl)-1-(4-fluorophenyl)-4-isopropoxy-2-oxo-1,2-dihydropyridine-3-carboxamide (95 mg, 49.4% yield) as a white solid. 1H NMR (400 MHz, DMSO-d6): δ 11.05 (s, 1H), 10.52 (s, 1H), 8.30 (dd, J=12.6, 7.2 Hz, 1H), 8.18 (d, J=5.7 Hz, 1H), 7.87 (d, J=7.9 Hz, 1H), 7.68 (d, J=2.4 Hz, 1H), 7.51-7.48 (m, 3H), 7.35 (t, J=8.7 Hz, 2H), 6.72 (dd, J=5.7, 2.4 Hz, 1H), 6.55 (d, J=8.0 Hz, 1H); 4.85 (m, 1H), 2.34 (q, J=7.5 Hz, 2H), 1.31 (d, J=6.0 Hz, 6H), 0.99 (t, J=7.5 Hz, 3H); MS (ESI) m/z: 567.1 (M+H+).

1. customsparged with argon under sonication
2. filtrationThe solids were collected by filtration
3. washwashed with DCM and MeCN
4. customThe filtrate was evaporated
5. customthe residue purified by silica gel chromatography (0-100% EtOAc/DCM)