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 record

ord-537ce69c4cb8468a82dd55183f686b2e

Source dataset

uspto-grants-2015_06

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09051321B2