Pentafluorophenol → 2-Anilino-4-(2,5-dioxopyrrolidin-1-ylmethyl)pyrimidine

Participants

Reaction Steps

1-[3-(Dimethylamino)propyl]3-ethylcarbodiimnide hydrochloride (4.44 g, 22 mmol) was added in one portion to a stirred mixture of 4-{[(2-anilinopyrimidin-4-yl)methyl]amino}-4-oxobutanoic acid (Method 13; 6.0 g, 20mmol) and pentafluorophenol (4.05 g, 22 mmol) in DMF (180 ml) under nitrogen. The reaction was stirred at ambient temperature under nitrogen for 20 hours and then the reaction mixture was concentrated by evaporation. The residue was partitioned between EtOAc and water. The layers were separated and the organic layer washed with water (2×) and saturated brine, dried (Na2SO4) and the volatiles removed by evaporation. The crude pentafluoroester was stirred in dry TBF (218 ml) under nitrogen at 0° C. and sodium hydride (528 mg of a 60 % dispersion in oil, 22 mmol) added in one portion. The reaction mixture was stirred at 0° C. for 15 minutes and then 72 hours at ambient temperature. Acetic acid (1.32 ml) was added and the reaction mixture was concentrated by evaporation. The residue was partitioned between EtOAc and water and the layers separated. The organic layer was washed with dilute aqueous sodium hydrogen carbonate solution (2×), water and saturated brine, dried (Na2SO4) and the volatiles removed by evaporation. The crude product was purified by chromatography eluting with EtOAc/isohexane (60:40 and then 100:0). The purified product was triturated with isohexane, collected by filtration and dried to give the title compound (2.65 g, 47%) as a white solid. NMR: 2.75 (s, 4H), 4.55 (s, 2H), 6.75 (d, 1H), 6.93 (t, 1H), 7.25 (t, 2H), 7.64 (d, 2H), 8.37 (d, 1H), 9.53 (s, 1H); m/z 283.

Provenance & Evidence