8-Hydroxyquinoline → HCID 24983815, compound

HRID 1887310Notes

Reaction equation

HRID 1887310 reaction equation
[CH2:1]([NH:8][C:9]([C:11]1[CH:15]=[C:14](Br)[S:13][CH:12]=1)=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH2:17]([O:24][C:25]1[CH:30]=[CH:29][NH:28][C:27](=[O:31])[CH:26]=1)[C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1.OC1C=CC=C2C=1N=CC=C2.C(=O)([O-])[O-].[K+].[K+]>CN(C)C=O.C(OCC)(=O)C.[Cu]I>[CH2:1]([NH:8][C:9]([C:11]1[CH:15]=[C:14]([N:28]2[CH:29]=[CH:30][C:25]([O:24][CH2:17][C:18]3[CH:19]=[CH:20][CH:21]=[CH:22][CH:23]=3)=[CH:26][C:27]2=[O:31])[S:13][CH:12]=1)=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

8

Reactant 4

HCID 19238-HydroxyquinolineHCID 11430Potassium CarbonateHCID 36077244-Benzyloxy-2(1H)-pyridoneHCID 43424405HCID 43424405, compound

Product 1

HCID 24983815HCID 24983815, compoundYield 18%

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
130 °C

Procedure

A mixture of N-benzyl-5-bromothiophene-3-carboxamide (0.57 g, 1.91 mmol), 4-(benzyloxy)pyridin-2(1H)-one (0.42 g, 2.10 mmol), copper(I) iodide (0.055 g, 0.29 mmol), 8-hydroxyquinoline (0.042 g, 0.29 mmol) and potassium carbonate (0.40 g, 2.87 mmol) in N,N-dimethylformamide (15 mL) was stirred at 130° C. for 17 h under nitrogen atmosphere. The reaction mixture was allowed to cool to ambient temperature, and then diluted with ethyl acetate (50 mL). The organic layer was washed with water (2×25 mL), dried over sodium sulfate and filtered. The filtrate was concentrated in vacuo and the residue was purified by column chromatography eluting with 10-80% ethyl acetate in hexanes to afford the title compound as a white solid (0.14 g, 18%): mp 162-163° C.; 1H NMR (300 MHz, DMSO-d6) δ 8.55 (t, J=6.0 Hz, 1H), 8.07 (d, J=7.9 Hz, 1H), 8.00 (d, J=1.5 Hz, 1H), 7.71 (d, J=1.5 Hz, 1H), 7.49-7.20 (m, 10H), 6.26 (dd, J=7.8, 2.7 Hz, 1H), 6.11 (d, J=2.7 Hz, 1H), 5.16 (s, 2H), 4.46 (d, J=6.0 Hz, 2H); MS (ES+) m/z 417.2 (M+1).

Workup

  1. temperatureto cool to ambient temperature
  2. washThe organic layer was washed with water (2×25 mL)
  3. dry with materialdried over sodium sulfate
  4. filtrationfiltered
  5. concentrationThe filtrate was concentrated in vacuo
  6. customthe residue was purified by column chromatography
  7. washeluting with 10-80% ethyl acetate in hexanes

Sources & evidence

ORD record
ord-68759251b13f48bf9a31e684f067d573
Source dataset
uspto-grants-2013_08
Patent number
US08501746B2

Reaction notes

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