O-(2,2,2-Trifluoroethyl)hydroxylamine hydrochloride → 6-[(E)-3-[3-[(Z)-C-methyl-N-(2,2,2-trifluoroethoxy)carbonimidoyl]azetidin-1-yl]-3-oxoprop-1-enyl]-3,4-dihydro-1H-1,8-naphthyridin-2-one

2,2,2-Trifluoroethoxyamine hydrochloride (37 mg, 0.24 mmol) was added to a solution of (E)-6-(3-(3-acetylazetidin-1-yl)-3-oxoprop-1-enyl)-3,4-dihydro-1,8-naphthyridin-2(1H)-one (50 mg, 0.16 mmol) in methanol (4 mL). The reaction mixture was stirred at room temperature for 3 hours. After concentration to dryness the residue was diluted by addition of dichloromethane (50 mL) and saturated sodium bicarbonate solution (10 mL). The aqueous phase was extracted with dichloromethane (2×40 mL). The combined organic phases were washed with a saturated solution of sodium chloride (1×20 mL), dried over sodium sulfate, filtered and concentrated to dryness. The residue was purified by chromatography on silica gel using ethyl acetate/methanol (95:5) as eluent to obtain the title product as a white solid (47 mg, 50%).

1. concentrationAfter concentration to dryness the residue
2. additionwas diluted by addition of dichloromethane (50 mL) and saturated sodium bicarbonate solution (10 mL)
3. extractionThe aqueous phase was extracted with dichloromethane (2×40 mL)
4. washThe combined organic phases were washed with a saturated solution of sodium chloride (1×20 mL)
5. dry with materialdried over sodium sulfate
6. filtrationfiltered
7. concentrationconcentrated to dryness
8. customThe residue was purified by chromatography on silica gel

ORD-Eintrag

ord-9755dfe6fdc947ddaa5ce9c38564f4a0

Quelldatensatz

uspto-grants-2014_09

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US08846711B2