Hydrochloric Acid → HCID 44137813, compound

Participants

Reaction Steps

To a solution of N-(4-(3-chloro-2-(diphenylmethyleneamino)pyridin-4-yloxy)-3-fluorophenyl)-5-(4-fluorophenyl)-4-oxo-1,4-dihydropyridine-3-carboxamide (5.0 g, 7.90 mmol) in DMF (50 mL) at room temperature were added potassium carbonate (7.64 g, 55.3 mmol) and di-tert-butyl chloromethyl phosphate (9.19 g, 35.5 mmol, see: PCT WO 2005/090367). The reaction mixture was stirred at room temperature for 2 days. The mixture was then diluted with EtOAc (250 mL), washed with water (200 mL), aq 10% LiCl (3×250 mL), dried over Na2SO4, and filtered. The filtrate was concentrated to give a residue, which was dissolved in EtOH (160 mL). To this stirred solution, was added water (60 mL), followed by the slow addition of conc. HCl (40 mL). The resulting mixture was stirred at rt for 15 min, and then allowed to stand overnight. HPLC analysis indicated that the reaction was complete. The solid was collected by filtration, rinsed with 50% EtOH/H2O (5×), water, EtOH, and EtOAc. The solid was dried under vacuum to give the title compound (4.3 g, 93%) as a white solid. 1H NMR (TFA-d) δ 9.60 (s, 1H), 8.79 (s, 1 H), 7.80-7.90 (m, 2H), 7.65-7.75 (m, 2H), 7.57 (d, 1H, J=7.04 Hz), 7.45 (t, 1H, J=6.80 Hz), 7.25-7.33 (m, 2H), 6.50 (d, 1H, J=5.92 Hz), 6.39 (d, 2H, J=9.88 Hz); MS (ESI+) m/z 579 (M+H)+.

Provenance & Evidence