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

HRID 83048Notes

Reaction equation

HRID 83048 reaction equation
Cl.[Br:2][C:3]1[CH:4]=[C:5]([CH2:8][O:9][CH:10]2[CH2:13][NH:12][CH2:11]2)[S:6][CH:7]=1.CCN=C=NCCCN(C)C.C1C=CC2N(O)N=NC=2C=1.C(N(C(C)C)CC)(C)C.Cl.[O:45]=[C:46]1[NH:55][C:54]2[N:53]=[CH:52][C:51](/[CH:56]=[CH:57]/[C:58](O)=[O:59])=[CH:50][C:49]=2[CH2:48][CH2:47]1>CN(C)C=O.O.C(OCC)(=O)C>[Br:2][C:3]1[CH:4]=[C:5]([CH2:8][O:9][CH:10]2[CH2:11][N:12]([C:58](=[O:59])/[CH:57]=[CH:56]/[C:51]3[CH:50]=[C:49]4[C:54](=[N:53][CH:52]=3)[NH:55][C:46](=[O:45])[CH2:47][CH2:48]4)[CH2:13]2)[S:6][CH:7]=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 67154616HCID 67154616, compound

Product 1

HCID 52950747(E)-6-(3-(3-((4-Bromothiophen-2-yl)methoxy)azetidin-1-yl)-3-oxoprop-1-enyl)-3,4-dihydro-1,8-naphthyridin-2(1H)-oneYield 62.3%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

3-((4-Bromothiophen-2-yl)methoxy)-azetidine hydrochloride (168 mg, 0.59 mmol), EDCI (113 mg, 0.59 mmol), HOBt (82 mg, 0.59 mmol) and diisopropylethylamine (171 μL, 1.00 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 (100 mg, 0.39 mmol) in dimethylformamide (10 mL) at room temperature. The reaction mixture was stirred overnight 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 triturated in diethyl ether to afford a pale yellow solid (109 mg, 62%).

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 triturated in diethyl ether

Sources & evidence

ORD record
ord-cd4cb29e364741eba5741093537441b4
Source dataset
uspto-grants-2014_09
Patent number
US08846711B2

Reaction notes

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