1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → 6-{(1E)-3-[2-(5-Methyl-1,2,4-oxadiazol-3-yl)piperidin-1-yl]-3-oxoprop-1-en-1-yl}-3,4-dihydro-1,8-naphthyridin-2(1H)-one

HRID 633891Notes

Reaction equation

HRID 633891 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]1[O:24][N:23]=[C:22]([CH:25]2[CH2:30][CH2:29][CH2:28][CH2:27][NH:26]2)[N:21]=1.CCN(C(C)C)C(C)C.CCN=C=NCCCN(C)C>CC(C)=O.CN(C=O)C>[CH3:19][C:20]1[O:24][N:23]=[C:22]([CH:25]2[CH2:30][CH2:29][CH2:28][CH2:27][N:26]2[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)[N:21]=1

Participants

7

Reactant 4

HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 81531DiisopropylethylamineHCID 509881752-(5-Methyl-1,2,4-oxadiazol-3-yl)piperidine hydrochlorideHCID 66905305(E)-3-(7-oxo-5,6,7,8-tetrahydro-1,8-naphthyridin-3-yl)acrylic Acid Hydrochloride

Product 1

HCID 529504856-{(1E)-3-[2-(5-Methyl-1,2,4-oxadiazol-3-yl)piperidin-1-yl]-3-oxoprop-1-en-1-yl}-3,4-dihydro-1,8-naphthyridin-2(1H)-oneYield 34%

Reagents, catalysts & solvents 2

HCID 180AcetoneSolventHCID 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 (30 mg, 0.12 mmol), DMF (3 mL), 2-(5-methyl-1,2,4-oxadiazol-3-yl)piperidine hydrochloride (29 mg, 0.14 mmol; which may be prepared as described in Step 3), DIPEA (48 μL, 0.28 mmol) and EDAC (27 mg, 0.14 mmol). The reaction mixture was stirred at room temperature overnight and concentrated to dryness. The residue was purified on preparative TLC (eluent: dichloromethane/NH3 7N in MeOH, 2.5%) to give an oil. This oil was taken up in acetone, diethyl ether and concentrated. The resulting wax was finally dissolved in dichloromethane, concentrated and dried to give the title compound (15 mg, 34%) as a yellow solid.

Workup

  1. concentrationconcentrated to dryness
  2. customThe residue was purified on preparative TLC (eluent: dichloromethane/NH3 7N in MeOH, 2.5%)
  3. customto give an oil
  4. concentrationdiethyl ether and concentrated
  5. dissolutionThe resulting wax was finally dissolved in dichloromethane
  6. concentrationconcentrated
  7. customdried

Sources & evidence

ORD record
ord-c4e301156de54911b412e233c850563c
Source dataset
uspto-grants-2016_04
Patent number
US09321769B2

Reaction notes

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