Acetamide, 2-cyano-N-phenyl- → tert-butyl 3-cyano-2-oxo-1-phenyl-1,2,7,8-tetrahydro-1,6-naphthyridine-6(5H)-carboxylate

HRID 885069Notes

Reaction equation

HRID 885069 reaction equation
[C:1]([CH2:3][C:4]([NH:6][C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1)=[O:5])#[N:2].[Li+].CC([N-]C(C)C)C.[C:21]([O:25][C:26]([N:28]1[CH2:33][CH2:32][C:31](=O)/[C:30](=[CH:35]/N(C)C)/[CH2:29]1)=[O:27])([CH3:24])([CH3:23])[CH3:22]>C1COCC1>[C:1]([C:3]1[C:4](=[O:5])[N:6]([C:7]2[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=2)[C:31]2[CH2:32][CH2:33][N:28]([C:26]([O:25][C:21]([CH3:24])([CH3:23])[CH3:22])=[O:27])[CH2:29][C:30]=2[CH:35]=1)#[N:2]

Participants

5

Reactant 3

HCID 69296Acetamide, 2-cyano-N-phenyl-HCID 2724682Lithium diisopropylamideHCID 10610967tert-butyl (3E)-3-[(dimethylamino)methylidene]-4-oxopiperidine-1-carboxylate

Product 1

HCID 58026066tert-butyl 3-cyano-2-oxo-1-phenyl-1,2,7,8-tetrahydro-1,6-naphthyridine-6(5H)-carboxylate

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

2-Cyano-N-phenylacetamide (820 mg) in THF (20 mL) was treated with LDA (4.4 mL, 1.8M solution in heptane/THF/ethylbenzene) at −78° C. for 1 h, before (E)-tert-butyl-3-((dimethylamino)methylene)-4-oxopiperidine-1-carboxylate (1 g) was added. The reaction mixture was allowed to warm to room temperature, and quenched with saturated NaHCO3 aqueous solution (20 mL). The aqueous solution was extracted with EtOAc (3×20 mL) and the combined organic layer was dried over MgSO4. Concentration under vacuum provided a residue which was purified by HPLC to afford tert-butyl 3-cyano-2-oxo-1-phenyl-1,2,7,8-tetrahydro-1,6-naphthyridine-6(5H)-carboxylate. LCMS: m/z 352.2 (M+H)+, 1.63 min (method 8). 1H NMR (500 MHz, DMSO-d6) δ ppm 8.19 (s, 1H) 7.48-7.57 (m, 3H) 7.33 (d, J=7.02 Hz, 2H) 4.33 (s, 2H) 3.44 (t, J=5.65 Hz, 2H) 2.19 (t, J=5.80 Hz, 2H) 1.39 (s, 9H).

Workup

  1. additionwas added
  2. customquenched with saturated NaHCO3 aqueous solution (20 mL)
  3. extractionThe aqueous solution was extracted with EtOAc (3×20 mL)
  4. dry with materialthe combined organic layer was dried over MgSO4
  5. concentrationConcentration under vacuum
  6. customprovided a residue which
  7. customwas purified by HPLC

Sources & evidence

ORD record
ord-6270a4a58200482ea49ccd8f75c95c42
Source dataset
uspto-grants-2012_08
Patent number
US08242124B2

Reaction notes

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