Triethylamine → HCID 131730221, compound

Participants

Reaction Steps

After dissolving N-{4-[(2-aminopyridin-4-yl)oxy]-2,5-difluorophenyl}-N′-(4-fluorophenyl)cyclopropane-1,1-dicarboxyamide (100.0 mg) in tetrahydrofuran (1 ml) under a nitrogen atmosphere, triethylamine (0.0630 ml) and phenyl chloroformate (0.0624 ml) were added dropwise in that order at 0° C. and the mixture was stirred for 30 minutes. Ethyl acetate (5 ml) and a saturated aqueous solution of sodium hydrogencarbonate (5 ml) were then added to the reaction mixture which was then stirred. The organic layer was separated, washed with brine and dried over anhydrous sodium sulfate. The solvent was concentrated under reduced pressure. The residue was then dissolved in N,N-dimethylformamide (1.0 ml). After adding 3-hydroxyazetidine hydrochloride (99.0 mg) and triethylamine (0.315 ml) at room temperature, the mixture was stirred for 22 hours and 5 minutes. The reaction mixture was partitioned between ethyl acetate (10 ml) and a saturated aqueous solution of sodium hydrogencarbonate (5 ml). The organic layer was washed with brine and dried over anhydrous sodium sulfate. The solvent was concentrated under reduced pressure. Ethyl acetate (1 ml) and heptane (1 ml) were then added to the obtained residue to precipitate a solid, and the solid was collected by filtration. The obtained solid was purified by silica gel column chromatography (Fuji Silysia NH, eluent: ethyl acetate, then ethyl acetate:methanol=10:1) and the fractions containing the target compound were concentrated under reduced pressure to give the title compound (71.1 mg, 58%) as white powder.

Provenance & Evidence