Triethylamine → HCID 16117291, compound

Participants

Reaction Steps

N-{4-[(2-Aminopyridin-4-yl)oxy]-2,5-difluorophenyl}-N′-(4-fluorophenyl)cyclopropane-1,1-dicarboxamide (100.0 mg) was dissolved in tetrahydrofuran (2.0 ml) under a nitrogen atmosphere, triethylamine (0.0630 ml) and phenyl chloroformate (0.0624 ml) were added dropwise at 0° C., followed by stirring for 30 min. The reaction mixture was stirred after addition of ethyl acetate (5 ml) and saturated sodium hydrogencarbonate (5 ml). The organic layer was separated, washed with brine, dried over anhydrous sodium sulfate and filtered it. The solvent was concentrated under reduced pressure. The residue was dissolved in N,N-dimethylformamide (2.0 ml). (R)-(−)-3-Pyrrolidinol hydrochloride (112.0 mg) and triethylamine (0.315 ml) were added at room temperature under a nitrogen atmosphere, followed by stirring 22 hr and 15 min. The reaction mixture was partitioned between ethyl acetate (10 ml) and saturated 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 the resultant residue was added heptane:ethyl acetate=10:1 to suspend a solid. The solid was collected by filtration to provide the titled compound as white powder (76.4 mg, 61%).

Provenance & Evidence