1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → (E)-6-(3-(3-(Benzo[b]thiophen-2-ylmethoxy)azetidin-1-yl)-3-oxoprop-1-enyl)-3,4-dihydro-1,8-naphthyridin-2(1H)-one

HRID 83046Notes

Reaction equation

HRID 83046 reaction equation
Cl.[S:2]1[C:6]([CH2:7][O:8][CH:9]2[CH2:12][NH:11][CH2:10]2)=[CH:5][C:4]2[CH:13]=[CH:14][CH:15]=[CH:16][C:3]1=2.CCN=C=NCCCN(C)C.C1C=CC2N(O)N=NC=2C=1.C(N(C(C)C)CC)(C)C.Cl.[O:48]=[C:49]1[NH:58][C:57]2[N:56]=[CH:55][C:54](/[CH:59]=[CH:60]/[C:61](O)=[O:62])=[CH:53][C:52]=2[CH2:51][CH2:50]1>CN(C)C=O.O.C(OCC)(=O)C>[S:2]1[C:6]([CH2:7][O:8][CH:9]2[CH2:10][N:11]([C:61](=[O:62])/[CH:60]=[CH:59]/[C:54]3[CH:53]=[C:52]4[C:57](=[N:56][CH:55]=3)[NH:58][C:49](=[O:48])[CH2:50][CH2:51]4)[CH2:12]2)=[CH:5][C:4]2[CH:13]=[CH:14][CH:15]=[CH:16][C:3]1=2

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 67154657HCID 67154657, compound

Product 1

HCID 52950746(E)-6-(3-(3-(Benzo[b]thiophen-2-ylmethoxy)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-(Benzo[b]thiophen-2-ylmethoxy)-azetidine hydrochloride (136 mg, 0.76 mmol), EDCI (146 mg, 0.76 mmol), HOBt (103 mg, 0.76 mmol) and diisopropylethylamine (222 μL, 1.27 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 (130 mg, 0.51 mmol) in dimethylformamide (10 mL) at room temperature. The reaction mixture was stirred for 3 days. The reaction mixture was then diluted by addition of ethyl acetate (50 mL) and water (50 mL). The aqueous phase was extracted with ethyl acetate (3×100 mL) and dichloromethane (3×100 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. After trituration in acetone and methanol, the title product was obtained as a white solid (112 mg, 45%).

Workup

  1. extractionThe aqueous phase was extracted with ethyl acetate (3×100 mL) and dichloromethane (3×100 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-e42ff991d2d04a9a8e71ac03b5a555f4
Source dataset
uspto-grants-2014_09
Patent number
US08846711B2

Reaction notes

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