Potassium hydride → 4-(4-Amino-2,5-difluorophenoxy)pyridine-2-carboxamide

Participants

Reaction Steps

To a mixture of potassium hydride (30-35% dispersion in mineral oil, 1.9 g, 13.9 mmol) in DMF (30 mL) was added 4-amino-2,5-difluorophenol (1.7 g, 11.6 mmol) as a solution in DMF (5 mL). After one hour of stirring at ambient temperature, 4-chloropicolinamide (1.8 g, 11.6 mmol) was added and the reaction mixture was heated to 100° C. for 135 h. The mixture was cooled to room temperature, quenched with 10% aqueous lithium chloride and then extracted three times with EtOAc. The combined organic layers were dried (MgSO4), filtered and concentrated in vacuo. The resultant solid was partitioned between chloroform and water. The organic layer was washed with brine, dried (MgSO4), filtered and concentrated in vacuo to a solid (3.0 g, 98%). 1H NMR (DMSO-d6) δ 8.51-8.57 (m, 1H), 8.14 (br s, 1H), 7.74 (br s, 1H), 7.37-7.38 (m, 1H), 7.17-7.30 (m, 2H), 6.74-6.80 (m, 1H), 5.62 (s, 2H); MS(ESI+) m/z 266 (M+H)+.

Provenance & Evidence