Pyridine → HCID 71575770, compound

Participants

Reaction Conditions

Reaction Steps

A solution of Example B1, (5.2 g, 18.8 mmol) in SOCl2 (50 mL, 685 mmol) was heated at 60° C. for 2 h. The mixture was azeotroped with toluene and concentrated to dryness. The solid was dissolved in DCM (150 mL), cooled to 0° C. and treated with a solution of Example A3 (5 g, 17.1 mmol) and pyridine (0.14 mL, 1.74 mmol) in DCM (100 mL) over 20 min. The reaction mixture was stirred at 0° C. for 10 min and then warmed to RT for 2 h. Water (5 mL) was added and the mixture was concentrated in vacuo. The residue was triturated with water (200 mL) and the solids were collected by filtration, washed with water and dried under vacuum. The solids were dissolved in DCM (400 mL), washed with saturated NaHCO3 (2×100 mL) and brine (100 mL), dried over Na2SO4, and concentrated to dryness. The solids were triturated with hexanes/EtOAc (1:1), collected by filtration and dried under vacuum to give N-(2,5-difluoro-4-((2-propionamidopyridin-4-yl)oxy)phenyl)-4-ethoxy-1-(4-fluorophenyl)-2-oxo-1,2-dihydropyridine-3-carboxamide (7.5 g, 82.4% yield). 1H NMR (400 MHz, DMSO-d6): δ 11.22 (s, 1H), 10.52 (s, 1H), 8.33 (dd, J=12.6, 7.2 Hz, 1H), 8.18 (d, J=5.7 Hz, 1H), 7.92 (d, J=7.8 Hz, 1H), 7.68 (d, J=2.4 Hz, 1H), 7.50-7.48 (m, 3H), 7.36 (t, J=8.7 Hz, 2H), 6.72 (dd, J=5.7, 2.4 Hz, 1H), 6.55 (d, J=7.9 Hz, 1H), 4.28 (q, J=7.0 Hz, 2H), 2.33 (q, J=7.5 Hz, 2H), 1.34 (t, J=7.0 Hz, 3H), 0.99 (t, J=7.5 Hz, 3H); MS (ESI) m/z: 553.2 (M+H+).

Provenance & Evidence