1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → HCID 52950660, compound

HRID 633954Notes

Reaction equation

HRID 633954 reaction equation
Cl.[NH:2]1[CH2:5][CH:4]([O:6][CH2:7][C:8]2[S:12][CH:11]=[N:10][CH:9]=2)[CH2:3]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:58]=[C:57]([N:2]1[CH2:5][CH:4]([O:6][CH2:7][C:8]2[S:12][CH:11]=[N:10][CH:9]=2)[CH2:3]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

7

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 67154562HCID 67154562, compound

Product 1

HCID 52950660HCID 52950660, compoundYield 2%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

5-((Azetidin-3-yloxy)methyl)thiazole hydrochloride (113 mg, 0.54 mmol), EDCI (121 mg, 0.63 mmol), HOBt (87.7 mg, 0.63 mmol) and diisopropylethylamine (183 μL, 1.05 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 (107 mg, 0.42 mmol) in dimethylformamide (10 mL) at room temperature. The reaction mixture was stirred overnight then partitioned between ethyl acetate (30 mL) and water (20 mL). The aqueous layer was separated and extracted with ethyl acetate (2×20 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 (10:0 to 98:2) as eluent then on C18 using dichloromethane/methanol (98:2) as eluent. In order to reach the required purity, the residue was finally recrystallized in methanol to afford the title product as a white solid (2.8 mg, 2%).

Workup

  1. customthen partitioned between ethyl acetate (30 mL) and water (20 mL)
  2. customThe aqueous layer was separated
  3. extractionextracted with ethyl acetate (2×20 mL)
  4. washThe combined organic phases were washed with a saturated solution of sodium chloride (3×30 mL)
  5. dry with materialdried over sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated to dryness
  8. customThe residue was purified by chromatography on silica gel
  9. customthe residue was finally recrystallized in methanol

Sources & evidence

ORD record
ord-41b33cf02f924fd89d65c5c5fa64ddc7
Source dataset
uspto-grants-2016_04
Patent number
US09321769B2

Reaction notes

Loading…