1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → (E)-6-(3-(3-(Benzofuran-7-yloxy)azetidin-1-yl)-3-oxoprop-1-enyl)-3,4-dihydro-1,8-naphthyridin-2(1H)-one

HRID 83067Notes

Reaction equation

HRID 83067 reaction equation
Cl.[O:2]1[C:6]2[C:7]([O:11][CH:12]3[CH2:15][NH:14][CH2:13]3)=[CH:8][CH:9]=[CH:10][C:5]=2[CH:4]=[CH:3]1.CCN=C=NCCCN(C)C.C1C=CC2N(O)N=NC=2C=1.C(N(C(C)C)CC)(C)C.Cl.[O:47]=[C:48]1[NH:57][C:56]2[N:55]=[CH:54][C:53](/[CH:58]=[CH:59]/[C:60](O)=[O:61])=[CH:52][C:51]=2[CH2:50][CH2:49]1>CN(C)C=O.O.C(OCC)(=O)C>[O:2]1[C:6]2[C:7]([O:11][CH:12]3[CH2:15][N:14]([C:60](=[O:61])/[CH:59]=[CH:58]/[C:53]4[CH:52]=[C:51]5[C:56](=[N:55][CH:54]=4)[NH:57][C:48](=[O:47])[CH2:49][CH2:50]5)[CH2:13]3)=[CH:8][CH:9]=[CH:10][C:5]=2[CH:4]=[CH:3]1

Participants

9

Reactant 5

HCID 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 671547083-(Benzofuran-7-yloxy)-azetidine hydrochloride

Product 1

HCID 52950789(E)-6-(3-(3-(Benzofuran-7-yloxy)azetidin-1-yl)-3-oxoprop-1-enyl)-3,4-dihydro-1,8-naphthyridin-2(1H)-one

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

3-(Benzofuran-7-yloxy)-azetidine hydrochloride (190 mg, 0.84 mmol), EDCI (161 mg, 0.84 mmol), HOBt (113 mg, 0.84 mmol) and diisopropylethylamine (240 μL, 1.40 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 (143 mg, 0.56 mmol) in dimethylformamide (14 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 aqueous phase was separated and extracted with ethyl acetate (2×40 mL). The combined organic phases were washed with a saturated solution of sodium chloride (3×40 mL), dried over sodium sulfate, filtered and concentrated to dryness. The residue was purified by chromatography on silica gel using dichloromethane/methanol (1:0 to 95:5) as eluent. After trituration in diethyl ether and acetone, the title compound was obtained as a white solid (80 mg, 37%).

Workup

  1. customThe aqueous phase was separated
  2. extractionextracted with ethyl acetate (2×40 mL)
  3. washThe combined organic phases were washed with a saturated solution of sodium chloride (3×40 mL)
  4. dry with materialdried over sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated to dryness
  7. customThe residue was purified by chromatography on silica gel

Sources & evidence

ORD record
ord-739860ace9d244b2b3c944fe243f3fba
Source dataset
uspto-grants-2014_09
Patent number
US08846711B2

Reaction notes

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