Diisopropylethylamine → N-(4-(3-bromopyridin-4-yloxy)-2,5-difluorophenyl)-4-ethoxy-1-(4-fluorophenyl)-2-oxo-1,2-dihydropyridine-3-carboxamide

Participants

Reaction Steps

A suspension of 4-ethoxy-1-(4-fluorophenyl)-2-oxo-1,2-dihydropyridine-3-carbonyl chloride (freshly prepared from Example B2 (0.207 g, 0.747 mmol) using the method of Example 4) in THF (5 ml) was added to a 0° C. solution of Example A2 (0.15 g, 0.498 mmol) and N,N-diisopropylethylamine (0.870 ml, 4.98 mmol) in THF (5 ml). The mixture was allowed to warm to room temperature and stir overnight. Additional 4-ethoxy-1-(4-fluorophenyl)-2-oxo-1,2-dihydropyridine-3-carbonyl chloride [freshly prepared from Example B2 (0.207 g, 0.747 mmol)] was added and the mixture was stirred overnight at RT. Additional 4-ethoxy-1-(4-fluorophenyl)-2-oxo-1,2-dihydropyridine-3-carbonyl chloride [freshly prepared from Example B2 (414 mg, 0.996 mmol)] was added to the reaction mixture. After stirring for 3 h, the mixture was partitioned between CH2Cl2 and sat. Na2CO3 (aq) and extracted with sat. Na2CO3 (aq) (2×). The organic extract was dried and evaporated. The crude product was purified by silica gel chromatography (hexanes/EtOAc) to yield N-(4-(3-bromopyridin-4-yloxy)-2,5-difluorophenyl)-4-ethoxy-1-(4-fluorophenyl)-2-oxo-1,2-dihydropyridine-3-carboxamide (0.124 g, 44.4% yield). 1H NMR (400 MHz, DMSO-d6): δ 11.24 (s, 1H), 8.74 (s, 1H), 8.37 (m, 2H). 7.92 (d, J=7.8 Hz, 1H), 7.59 (dd. J=10.9, 7.4 Hz, 1H), 7.48 (dd, J=8.8, 4.9 Hz, 2H), 7.36 (t, J=8.7 Hz, 2H), 6.88 (d, J=5.6 Hz, 1H); 6.55 (d, J=7.9 Hz, 1H); 4.28 (q, J=7.0 Hz, 2H); 1.33 (t, J=7.0 Hz, 3H); MS (ESI) m/z: 560.1 (M+H+).

Provenance & Evidence