Dimethylamine, hydrochloride → Benzyl {4-[2-(3,3-dimethylureido)pyridin-4-yloxy]-2-fluorophenyl}carbamate

Participants

Reaction Steps

To a solution of benzyl [4-(2-aminopyridin-4-yloxy)-2-fluorophenyl]carbamate (163 mg, 0.461 mmol) in tetrahydrofuran (4.50 ml) was added triethylamine (0.128 ml, 0.918 mmol), and then phenyl chloroformate (0.0872 ml, 0.695 mmol) was added dropwise thereto, followed by stirring at room temperature for 10 min. The reaction mixture was concentrated under a reduced pressure to give a residue, to which N,N-dimethylformamide (2.0 ml), dimethylamine hydrochloride (188 mg, 2.31 mmol) and triethylamine (0.386 ml) were then added, followed by stirring at room temperature for 8 hrs. The reaction mixture was partitioned between ethyl acetate (50 ml) and water (30 ml). The organic layer was washed with brine (30 ml×3), and dried over anhydrous sodium sulfate. The solvent was evaporated to give a residue, which was then purified by silica gel column chromatography (eluent; ethyl acetate, then ethyl acetate:methanol=20:1) to provide the titled compound (165 mg, 47.5%) as pale yellow powder.

Provenance & Evidence