1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → 6-[(1E)-3-{3-[(2-Methylprop-2-en-1-yl)oxy]azetidin-1-yl}-3-oxoprop-1-en-1-yl]-3,4-dihydro-1,8-naphthyridin-2(1H)-one

HRID 633907Notes

Reaction equation

HRID 633907 reaction equation
Cl.[O:2]=[C:3]1[NH:12][C:11]2[N:10]=[CH:9][C:8](/[CH:13]=[CH:14]/[C:15]([OH:17])=O)=[CH:7][C:6]=2[CH2:5][CH2:4]1.Cl.[CH3:19][C:20](=[CH2:27])[CH2:21][O:22][CH:23]1[CH2:26][NH:25][CH2:24]1.CCN(C(C)C)C(C)C.CCN=C=NCCCN(C)C>CN(C1C=CN=CC=1)C.CN(C=O)C>[CH3:27][C:20](=[CH2:19])[CH2:21][O:22][CH:23]1[CH2:26][N:25]([C:15](=[O:17])/[CH:14]=[CH:13]/[C:8]2[CH:7]=[C:6]3[C:11](=[N:10][CH:9]=2)[NH:12][C:3](=[O:2])[CH2:4][CH2:5]3)[CH2:24]1

Participants

7

Reactant 4

HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 81531DiisopropylethylamineHCID 66905305(E)-3-(7-oxo-5,6,7,8-tetrahydro-1,8-naphthyridin-3-yl)acrylic Acid HydrochlorideHCID 671544963-[(2-Methylprop-2-en-1-yl)oxy]azetidine hydrochloride

Product 1

HCID 529505256-[(1E)-3-{3-[(2-Methylprop-2-en-1-yl)oxy]azetidin-1-yl}-3-oxoprop-1-en-1-yl]-3,4-dihydro-1,8-naphthyridin-2(1H)-oneYield 16.5%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6228DimethylformamideSolvent

Procedure

A 16 mL vial flask was successively charged with (2E)-3-(7-oxo-5,6,7,8-tetrahydro-1,8-naphthyridin-3-yl)acrylic acid hydrochloride (60 mg, 0.24 mmol), DMF (5.8 mL), 3-[(2-methylprop-2-en-1-yl)oxy]azetidine hydrochloride (78 mg, 0.48 mmol; which may be prepared as described in Step 2), DIPEA (119 μL, 0.72 mmol), DMAP (2.4 mg, 0.02 mmol) and EDAC (56 mg, 0.29 mmol). The reaction mixture was stirred at room temperature overnight and concentrated to dryness. The residue was precipitated in methanol/water and then filtered. The resulting solid was dissolved in chloroform and washed with water to give a beige solid. This solid was triturated in diethyl ether to give the title compound (13 mg, 16%) as a white solid.

Workup

  1. concentrationconcentrated to dryness
  2. customThe residue was precipitated in methanol/water
  3. filtrationfiltered
  4. dissolutionThe resulting solid was dissolved in chloroform
  5. washwashed with water
  6. customto give a beige solid
  7. customThis solid was triturated in diethyl ether

Sources & evidence

ORD record
ord-876f96c87beb4b5c9902240155b02bc0
Source dataset
uspto-grants-2016_04
Patent number
US09321769B2

Reaction notes

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