1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → HCID 52950705, compound

HRID 633990Notes

Reaction equation

HRID 633990 reaction equation
Cl.[F:2][C:3]([F:12])([F:11])[CH2:4][CH2:5][O:6][CH:7]1[CH2:10][NH:9][CH2:8]1.CCN=C=NCCCN(C)C.C1C=CC2N(O)N=NC=2C=1.C(N(C(C)C)CC)(C)C.Cl.[O:44]=[C:45]1[NH:54][C:53]2[N:52]=[CH:51][C:50](/[CH:55]=[CH:56]/[C:57](O)=[O:58])=[CH:49][C:48]=2[CH2:47][CH2:46]1>CN(C)C=O.O.C(OCC)(=O)C>[O:58]=[C:57]([N:9]1[CH2:10][CH:7]([O:6][CH2:5][CH2:4][C:3]([F:2])([F:11])[F:12])[CH2:8]1)/[CH:56]=[CH:55]/[C:50]1[CH:49]=[C:48]2[C:53](=[N:52][CH:51]=1)[NH:54][C:45](=[O:44])[CH2:46][CH2:47]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 67154599HCID 67154599, compound

Product 1

HCID 52950705HCID 52950705, compoundYield 39%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

3-(3,3,3-Trifluoropropoxy)azetidine hydrochloride (194 mg, 0.94 mmol), EDCI (181 mg, 0.94 mmol), HOBt (128 mg, 0.94 mmol) and diisopropylethylamine (274 μL, 1.57 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 (160 mg, 0.63 mmol) in dimethylformamide (15 mL) at room temperature. The reaction mixture was stirred overnight then diluted by addition of ethyl acetate (30 mL) and water (40 mL). The aqueous layer was separated and extracted with ethyl acetate (2×30 mL). The combined organic phases were washed with a saturated solution of sodium chloride (3×30 mL), dried over sodium sulfate, filtered and concentrated to dryness. The residue was purified by chromatography on silica gel using dichloromethane/methanol (98:2) as eluent. The residue was finally precipitated from methanol to afford the title product as a white solid (90 mg, 39%).

Workup

  1. customThe aqueous layer was separated
  2. extractionextracted with ethyl acetate (2×30 mL)
  3. washThe combined organic phases were washed with a saturated solution of sodium chloride (3×30 mL)
  4. dry with materialdried over sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated to dryness
  7. customThe residue was purified by chromatography on silica gel
  8. customThe residue was finally precipitated from methanol

Sources & evidence

ORD record
ord-cefbc838fd9045018fb9a4c5158e1c2a
Source dataset
uspto-grants-2016_04
Patent number
US09321769B2

Reaction notes

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