Triethylamine → HCID 59596916, compound

Participants

Reaction Steps

N-{4-[(2-Aminopyridin-4-yl)oxy]-2,3-difluorophenyl}-N′-(4-fluorophenyl)cyclopropane-1,1-dicarboxamide (84.0 mg) was dissolved in tetrahydrofuran (1 ml) under a nitrogen atmosphere, triethylamine (0.0530 ml) and phenyl chloroformate (0.0524 ml) were added dropwise at 0° C., followed by stirring for 20 min. The reaction mixture was stirred after addition of ethyl acetate (5 ml) and a saturated aqueous solution of sodium hydrogencarbonate (5 ml). The organic layer was separated, washed with brine, dried over anhydrous sodium sulfate and filtrated. The solvent was concentrated under reduced pressure. The residue was dissolved in N,N-dimethylformamide (2.0 ml). 3-hydroxyazetidine hydrochloride (83.3 mg) and triethylamine (0.265 ml) were added at room temperature under a nitrogen atmosphere, followed by stirring for 12 hr and 25 min. The reaction mixture was partitioned between ethyl acetate (10 ml) and a saturated aqueous solution of sodium hydrogencarbonate (5 ml). The organic layer was separated, washed with twice in water (10 ml) and brine in this order, and dried over anhydrous sodium sulfate. The solvent was concentrated under reduced pressure. The resultant residue was purified by silica gel column chromatography (Fuji Silysia NH, eluent; ethyl acetate, then ethyl acetate:methanol=10:1), and fractions containing the target compound were concentrated under reduced pressure to provide the titled compound as white powder (80.3 mg, 78%).

Provenance & Evidence