Potassium Iodide → Di-tert-butyl (3-(4-(3-chloro-2-(diphenylmethyleneamino)pyridin-4-yloxy)-3-fluorophenylcarbamoyl)-5-(4-fluorophenyl)-4-oxopyridin-1(4H)-yl)methyl phosphate

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 (1.0 g, 1.58 mmol) in DMF (10 mL) at room temperature were added Cs2CO3 (1.3 g, 3.95 mmol), potassium iodide (525 mg, 3.16 mmol) and then di-tert-butyl chloromethyl phosphate (1.2 mL, 1.90 mmol: 2.0 M in DMF). The reaction mixture was stirred at room temperature for 26 h prior to being quenched by the addition of isopropyl acetate (10 mL) and cold water (50 mL). The organics were separated and washed with water (50 mL). The solvent was swapped into isopropanol (10 mL) by continuous distillation at 86° C. The solution was cooled to 20° C. and a solid precipitated. The solid was collected by filtration and dried under vacuum at 60° C. for 12 h to give the desired product (0.98 g, 72%) as an off-white solid. MS (ESI+) m/z 856 (M+H)+.

Provenance & Evidence