Sodium Carbonate → 6-[3-(3-Acetyl-azetidin-1-yl)-3-oxo-propenyl]-3,4-dihydro-1H-[1,8]naphthyridin-2-one

HRID 634008Notes

Reaction equation

HRID 634008 reaction equation
OC(C(F)(F)F)=O.[NH:8]1[CH2:11][CH:10]([C:12](=[O:14])[CH3:13])[CH2:9]1.CCN=C=NCCCN(C)C.C1C=CC2N(O)N=NC=2C=1.C(N(C(C)C)CC)(C)C.Cl.[O:46]=[C:47]1[NH:56][C:55]2[N:54]=[CH:53][C:52](/[CH:57]=[CH:58]/[C:59](O)=[O:60])=[CH:51][C:50]=2[CH2:49][CH2:48]1.C(=O)([O-])[O-].[Na+].[Na+]>CN(C)C=O.O.C(OCC)(=O)C>[C:12]([CH:10]1[CH2:11][N:8]([C:59](=[O:60])[CH:58]=[CH:57][C:52]2[CH:51]=[C:50]3[C:55](=[N:54][CH:53]=2)[NH:56][C:47](=[O:46])[CH2:48][CH2:49]3)[CH2:9]1)(=[O:14])[CH3:13]

Participants

10

Reactant 6

HCID 10340Sodium CarbonateHCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 66905305(E)-3-(7-oxo-5,6,7,8-tetrahydro-1,8-naphthyridin-3-yl)acrylic Acid HydrochlorideHCID 866729861-(Azetidin-3-yl)ethan-1-one; trifluoroacetic acid

Product 1

HCID 671546786-[3-(3-Acetyl-azetidin-1-yl)-3-oxo-propenyl]-3,4-dihydro-1H-[1,8]naphthyridin-2-oneYield 50.1%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

1-Azetidin-3-yl-ethanone TFA (700 mg, 3.54 mmol), EDCI (676 mg, 3.54 mmol), HOBt (477 mg, 3.54 mmol) and diisopropylethylamine (2.1 mL, 11.8 mmol) were successively added to a solution of (E)-3-(7-oxo-5,6,7,8-tetrahydro-1,8-naphthyridin-3-yl)-acrylic acid hydrochloride (600 mg, 2.36 mmol) in dimethylformamide (15 mL) at room temperature. The reaction mixture was stirred overnight. The reaction mixture was then diluted by addition of ethyl acetate (40 mL) and water (40 mL). The organic layer was discarded and the aqueous layer was basified with an aqueous solution of saturated sodium carbonate until pH=12 and finally extracted with ethyl acetate (2×50 mL). The combined organic phases were washed with a saturated solution of sodium chloride (3×50 mL), dried over sodium sulfate and concentrated to dryness. The residue was purified by chromatography on silica gel using dichloromethane/methanol (1:0 to 95:5) as eluent to obtain the title compound as a white solid (354 mg, 50%).

Workup

  1. extractionfinally extracted with ethyl acetate (2×50 mL)
  2. washThe combined organic phases were washed with a saturated solution of sodium chloride (3×50 mL)
  3. dry with materialdried over sodium sulfate
  4. concentrationconcentrated to dryness
  5. customThe residue was purified by chromatography on silica gel

Sources & evidence

ORD record
ord-192accc309d244059c7e4e97445d0c36
Source dataset
uspto-grants-2016_04
Patent number
US09321769B2

Reaction notes

Loading…