Acetamide → N-(4-((2-acetamidopyridin-4-yl)oxy)-2,5-difluorophenyl)-4-ethoxy-1-(4-fluorophenyl)-2-oxo-1,2-dihydropyridine-3-carboxamide

Participants

Reaction Conditions

Reaction Steps

A mixture of N-(4-((2-chloropyridin-4-yl)oxy)-2,5-difluorophenyl)-4-ethoxy-1-(4-fluorophenyl)-2-oxo-1,2-dihydropyridine-3-carboxamide (36 g, 69.9 mmol), acetamide (12.4 g, 209 mmol), Xantphos (4 g, 6.9 mmol), Cs2CO3 (45.5 g, 140 mmol) and Pd2(dba)3 (3.84 g, 4.2 mmol) in dioxane (500 mL) was heated at 100° C. under nitrogen for 2 h. The reaction mixture was cooled to RT, filtered to remove inorganic salts, and concentrated under vacuum. The residue was treated with water (300 mL) and extracted with EtOAc (3×400 mL). The combined organics were washed with brine, dried over Na2SO4 and concentrated dryness. The residue was purified by silica gel chromatography to afford N-(4-((2-acetamidopyridin-4-yl)oxy)-2,5-difluorophenyl)-4-ethoxy-1-(4-fluorophenyl)-2-oxo-1,2-dihydropyridine-3-carboxamide (15 g, 44% yield). 1H NMR (400 MHz, DMSO-d6): 11.23 (s, 1 H), 10.60 (s, 1 H), 8.34 (dd, J=12.8, 7.2 Hz, 1 H), 8.20 (d, J=5.6 Hz, 1 H), 7.94 (d, J=8.0 Hz, 1 H), 7.68 (s, 1 H), 7.56-7.51 (m, 3 H), 7.40-7.36 (m, 2 H), 6.73 (dd, J=5.6, 2.4 Hz, 1 H), 6.56 (d, J=8.0 Hz, 1 H), 4.30 (q, J=6.8 Hz, 2 H), 2.05 (s, 3 H), 1.35 (t, J=6.8 Hz, 3 H); MS (ESI) m/z: 539.1 (M+H+).

Provenance & Evidence