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

HRID 2172111Notes

Reaction equation

HRID 2172111 reaction equation
Cl.[F:2][C:3]([F:8])([F:7])[CH2:4][O:5][NH2:6].[C:9]([CH:12]1[CH2:15][N:14]([C:16](=[O:30])/[CH:17]=[CH:18]/[C:19]2[CH:20]=[C:21]3[C:26](=[N:27][CH:28]=2)[NH:25][C:24](=[O:29])[CH2:23][CH2:22]3)[CH2:13]1)(=O)[CH3:10]>CO>[O:30]=[C:16]([N:14]1[CH2:15][CH:12](/[C:9](=[N:6]\[O:5][CH2:4][C:3]([F:8])([F:7])[F:2])/[CH3:10])[CH2:13]1)/[CH:17]=[CH:18]/[C:19]1[CH:20]=[C:21]2[C:26](=[N:27][CH:28]=1)[NH:25][C:24](=[O:29])[CH2:23][CH2:22]2

Participants

4

Reactant 2

HCID 19853822O-(2,2,2-Trifluoroethyl)hydroxylamine hydrochlorideHCID 67154676(E)-6-(3-(3-acetylazetidin-1-yl)-3-oxoprop-1-enyl)-3,4-dihydro-1,8-naphthyridin-2(1H)-one

Product 1

HCID 529507506-[(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-oneYield 74.1%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

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%).

Workup

  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

Sources & evidence

ORD record
ord-537ce69c4cb8468a82dd55183f686b2e
Source dataset
uspto-grants-2015_06
Patent number
US09051321B2

Reaction notes

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