Tetrahydrofuran → tert-butyl (3S*,5R*)-3-[({2-tert-butyl-4-[(furan-2-ylmethyl)amino]pyrimidin-5-yl}carbonyl)(2-methylpropyl)amino]-5-(5-oxo-4,5-dihydro-1,2,4-oxadiazol-3-yl)piperidine-1-carboxylate

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Reaction Steps

Hydroxylamine hydrochloride (35 mg) was dissolved in THF (3 ml)-methanol (3 ml), triethylamine (0.07 ml) was added, and the mixture was stirred at room temperature for 1 hr. A solution of tert-butyl (3S*,5R*)-3-[({2-tert-butyl-4-[(furan-2-ylmethyl)amino]pyrimidin-5-yl}carbonyl)(2-methylpropyl)amino]-5-(2H-tetrazol-5-yl)piperidine-1-carboxylate (120 mg) in THF (3 ml) was further added, and the mixture was stirred at 60° C. for 3 hr. The reaction mixture was allowed to cool to room temperature, and diluted with water, and the mixture was extracted with ethyl acetate. The extract was dried over anhydrous magnesium sulfate, and concentrated under reduced pressure, and the residue was dissolved in tetrahydrofuran (5 ml). 1,1′-Carbonylbis(1H-imidazole) (72 mg) and 1,8-diazabicyclo[5.4.0]undec-7-ene (0.066 ml) were added and the mixture was stirred at room temperature for 30 min. The reaction mixture was concentrated under reduced pressure, diluted with ethyl acetate, washed with 0.5 M hydrochloric acid and saturated brine, and dried over anhydrous magnesium sulfate. The solution was concentrated under reduced pressure, and the residue was subjected to silica gel chromatography. The fraction eluted with ethyl acetate-hexane (10:95) to ethyl acetate was concentrated under reduced pressure to give the object compound (26.1 mg).

Provenance & Evidence