8-Hydroxyquinoline → HCID 57950282, compound

HRID 1020689Notes

Reaction equation

HRID 1020689 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:22][CH2:21][C:11]2[N:12]([CH3:20])[C:13]3[CH:14]=[C:15](Br)[CH:16]=[CH:17][C:18]=3[C:10]=2[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[CH3:23][O:24][C:25]1[CH:30]=[CH:29][C:28]([C:31]2[CH:36]=[CH:35][NH:34][C:33](=[O:37])[CH:32]=2)=[C:27]([CH3:38])[CH:26]=1.C([O-])([O-])=O.[Cs+].[Cs+].OC1C=CC=C2C=1N=CC=C2>CS(C)=O.[Cu](I)I>[CH3:23][O:24][C:25]1[CH:30]=[CH:29][C:28]([C:31]2[CH:36]=[CH:35][N:34]([C:15]3[CH:16]=[CH:17][C:18]4[C:10]5[CH2:9][N:8]([C:6]([O:5][C:1]([CH3:4])([CH3:3])[CH3:2])=[O:7])[CH2:22][CH2:21][C:11]=5[N:12]([CH3:20])[C:13]=4[CH:14]=3)[C:33](=[O:37])[CH:32]=2)=[C:27]([CH3:38])[CH:26]=1

Participants

7

Reactant 4

HCID 19238-HydroxyquinolineHCID 10796Cesium carbonateHCID 532177564-(4-Methoxy-2-methylphenyl)pyridin-2(1H)-oneHCID 57950375tert-Butyl 7-bromo-5-methyl-3,4-dihydro-1H-pyrido[4,3-b]indole-2(5H)-carboxylate

Product 1

HCID 57950282HCID 57950282, compoundYield 52.1%

Reagents, catalysts & solvents 2

HCID 83717Copper iodideCatalystHCID 679Dimethyl SulfoxideSolvent

Conditions

Temperature
130 °C

Procedure

tert-Butyl-7-bromo-5-methyl-3,4-dihydro-1H-pyrido[4,3-b]indole-2(5H)-carboxylate (0.35 g, 0.96 mmol), 4-(4-methoxy-2-methylphenyl)pyridin-2(1H)-one (0.21 g, 0.96 mmol) and Cs2CO3 (0.35 g, 1.1 mmol) were suspensed in DMSO (5.6 mL), and the resulting suspension was degassed under vacuum for 15 min. The system was then flushed with Ar, and 8-hydroxyquinoline (42 mg, 0.29 mmol) and copper iodide (0.22 g, 1.2 mmol) were added. The evacuation/Ar flushing process was repeated twice more, and the reaction mixture was heated at 130° C. for 18 h under N2. The suspension was cooled, diluted with 20% NH4OH/MeOH (10 mL) and stirred at ambient temperature for 30 min. The reaction was further diluted with CH2Cl2 (100 mL). The solution was filtered through silica gel and concentrated. The concentrate was diluted with CH2Cl2 and washed with brine (4×20 mL). The organic phase was dried over Na2SO4 and concentrated to dryness under reduced pressure. Flash column chromatography (12 g ISCO column, (1:1 hexanes/EtOAc)/(80:18:2 CH2Cl2/MeOH/NH4OH), 100:0 for 5 column volumes, increased to 50:50 over 20 column volumes and then hold for 5 column volumes, increase to 0:100 over 10 column volumes and hold for 5 column volumes) gave the title compound (0.25 g, 52%) as a yellow film: 1H NMR (500 MHz, CDCl3) δ 7.54 (d, J=8.0 Hz, 1H), 7.42 (d, J=6.5 Hz, 1H), 7.39 (d, J=1.5 Hz, 1H), 7.22 (d, J=8.0 Hz, 1H), 7.10 (d, J=7.0 Hz, 1H), 6.82-6.80 (m, 2H), 6.60 (d, J=1.5 Hz, 1H), 6.24 (dd, J=6.5, 1.5 Hz, 1H), 4.67-4.65 (m, 2H), 3.86-3.83 (m, 5H), 3.65 (s, 3H), 2.93 (m, 3H), 2.82-2.84 (m, 2H), 1.50 (s, 9H).

Workup

  1. customthe resulting suspension was degassed under vacuum for 15 min
  2. additionwere added
  3. customThe evacuation/Ar flushing process
  4. temperatureThe suspension was cooled
  5. additiondiluted with 20% NH4OH/MeOH (10 mL)
  6. additionThe reaction was further diluted with CH2Cl2 (100 mL)
  7. filtrationThe solution was filtered through silica gel
  8. concentrationconcentrated
  9. additionThe concentrate was diluted with CH2Cl2
  10. washwashed with brine (4×20 mL)
  11. dry with materialThe organic phase was dried over Na2SO4
  12. concentrationconcentrated to dryness under reduced pressure
  13. temperatureFlash column chromatography (12 g ISCO column, (1:1 hexanes/EtOAc)/(80:18:2 CH2Cl2/MeOH/NH4OH), 100:0 for 5 column volumes, increased to 50:50 over 20 column volumes
  14. temperatureincrease to 0:100 over 10 column volumes

Sources & evidence

ORD record
ord-d5cfcbbc94ee4f159c8af17d36e33ff0
Source dataset
uspto-grants-2014_05
Patent number
US08716308B2

Reaction notes

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