1-Hydroxybenzotriazole → (2E)-3-(4-Chlorophenyl)-N-[(1S)-2-oxo-2-[[2-oxo-2-[4-(3,3,3-trifluoropropyl)-1-piperazinyl]ethyl]amino]-1-(2-pyridylmethyl)ethyl]-2-propenamide

To a mixture of [[(2S)-2-[[(2E)-3-(4-chlorophenyl)-2propenoyl]amino]-3-(2-pyridyl)propanoyl]amino]acetic acid (38.8 g), 1-(3,3,3-trifluoropropyl)piperazine dihydrochloride (25.5 g), 1-hydroxybenzotriazole (14.9 g) and 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (21.1 g) in N,N-dimethylformamide (250 ml) was added dropwise N,N-diisopropylethylamine (38.3 ml) at 10° C. over 50 minutes. The mixture was warmed to room temperature and stirred for 2 hours. The reaction mixture was poured into ice-cold saturated aqueous sodium hydrogencarbonate solution (750 ml). The mixture was extracted three times with ethyl acetate (total 2500 ml) and washed successively with water (500 ml×3) and brine (200 ml). The organic layer was dried over anhydrous magnesium sulfate and concentrated. The residue was purified by silica gel column chromatography (eluent; 12% methanol in ethyl acetate) to give the title compound (37.0 g) as a white amorphous solid, which was recrystallized from ethyl acetate.

1. extractionThe mixture was extracted three times with ethyl acetate (total 2500 ml)
2. washwashed successively with water (500 ml×3) and brine (200 ml)
3. dry with materialThe organic layer was dried over anhydrous magnesium sulfate
4. concentrationconcentrated
5. customThe residue was purified by silica gel column chromatography (eluent; 12% methanol in ethyl acetate)

ORD 기록

ord-4bf1da8568d74c4eaca8241ffdb7a859

출처 데이터셋

uspto-grants-2004_11

DOI

10.6084/m9.figshare.5104873.v1

특허 번호

US06825200B1