Diisopropylethylamine → HCID 24788500, compound

Participants

Reaction Steps

N,N-Diisopropylethylamine (0.249 ml) was added to a mixture of benzyl 1-({[4-({2-[(phenoxycarbonyl)amino]pyridin-4-yl}oxy)-2,5-difluorophenyl]amino}carbonyl)cyclopropanecarboxylate (200 mg), (R)-3-hydroxypyrrolidine hydrochloride (88.2 mg) and N-methylpyrrolidinone (4.0 ml) at room temperature under a nitrogen atmosphere, and the mixture was stirred for 5 hours. (R)-3-Hydroxypyrrolidine hydrochloride (44.1 mg) and N,N-diisopropylethylamine (0.125 ml) were added at room temperature, and the mixture was stirred for 15 hours and 40 minutes. A saturated aqueous solution of sodium hydrogencarbonate (20 ml) was added to the mixture to quench the reaction, and the mixture was partitioned after the addition of ethyl acetate and tetrahydrofuran (1:1) (50 ml) and (30 ml). The organic layer was washed with brine (30 ml), and dried over anhydrous magnesium sulfate. The desiccant was removed by filtration, and the filtrate 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). The fractions containing the target compound were concentrated under reduced pressure to give the title compound (178.2 mg, 90%) as a white solid.

Provenance & Evidence