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 2171991Notes

Reaction equation

HRID 2171991 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-7474788805714fddb79b0f470a9c86c2
Source dataset
uspto-grants-2015_06
Patent number
US09051321B2

Reaction notes

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