1,4-Dioxane → 1-((S)-3-(4-(4-methyl-[1,4]-diazepan-1-yl)quinazolin-2-ylamino)pyrrolidin-1-yl)-2-(4-trifluoromethoxyphenyl)ethanone

온도

80 °C

To a mixture of 2-chloro-4-(4-methyl-[1,4]-diazepan-1-yl)quinazoline (0.10 g), Pd2(dba)3 (0.017 g), (±)-BINAP (0.034 g), (S)-1-(3-aminopyrrolidin-1-yl)-2-(4-trifluoromethoxyphenyl)ethanone mono hydrochloride (0.13 g), and 1,4-dioxane (2 mL) was added sodium t-butoxide (0.10 g) under nitrogen atmosphere, and the mixture was stirred at 80° C. for 3 h. The reaction mixture was diluted with ethyl acetate and water, then the interlayer was removed by Celite filtration, and the organic layer was washed with saturated brine. The organic layer was dried with anhydrous magnesium sulfate, the desiccant was removed by filtration, the filtrate was concentrated under reduced pressure, and the residue was purified by silica gel column chromatography (NH silica gel, ethyl acetate−ethyl acetate/methanol=10:1) to obtain colorless amorphous 1-((S)-3-(4-(4-methyl-[1,4]-diazepan-1-yl)quinazolin-2-ylamino)pyrrolidin-1-yl)-2-(4-trifluoromethoxyphenyl)ethanone (0.12 g).

1. customthe interlayer was removed by Celite filtration
2. washthe organic layer was washed with saturated brine
3. dry with materialThe organic layer was dried with anhydrous magnesium sulfate
4. customthe desiccant was removed by filtration
5. concentrationthe filtrate was concentrated under reduced pressure
6. customthe residue was purified by silica gel column chromatography (NH silica gel, ethyl acetate−ethyl acetate/methanol=10:1)

ORD 기록

ord-6a80c4a4fdd54cd885c65615e6689943

출처 데이터셋

uspto-grants-2011_10

DOI

10.6084/m9.figshare.5104873.v1

특허 번호

US08044068B2