8-Hydroxyquinoline → HCID 57950370, compound

HRID 930768Notes

Reaction equation

HRID 930768 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)=[CH:27][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)=[CH:27][CH:26]=1

Participants

7

Reactant 4

HCID 19238-HydroxyquinolineHCID 10796Cesium carbonateHCID 109435304-(4-methoxyphenyl)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 57950370HCID 57950370, compoundYield 34.3%

Reagents, catalysts & solvents 2

HCID 83717Copper iodideCatalystHCID 679Dimethyl SulfoxideSolvent

Conditions

Temperature
133 °C

Procedure

tert-Butyl-7-bromo-5-methyl-3,4-dihydro-1H-pyrido[4,3-b]indole-2(5H)-carboxylate (0.19 g, 0.54 mmol), 4-(4-methoxyphenyl)pyridin-2(1H)-one (90 mg, 0.45 mmol) and Cs2CO3 (0.16 g, 0.49 mmol) were suspended in DMSO (2.0 mL) and degassed under vacuum for 15 min. The system was then flushed with Ar and 8-hydroxyquinoline (19 mg, 0.13 mmol) and copper iodide (0.10 g, 0.54 mmol) were added. The degassing/Ar flushing process was repeated twice more, and the reaction mixture was heated at 133° C. for 18 h under N2. The suspension was cooled, diluted with 20% NH4OH/MeOH (25 mL) and stirred at ambient temperature for 30 min. The suspension was further diluted with CH2Cl2 (100 mL). The solution was filtered through silica gel and concentrated under reduced pressure. The concentrate was diluted with CH2Cl2 and washed with brine (3×25 mL). The organic phase was dried over Na2SO4, filtered and concentrated to dryness. Flash column chromatography (12 g ISCO column, (1:1 hexanes/EtOAc)/(80:18:2 CH2Cl2/MeOH/NH4OH), 100:0 for 10 column volumes, increased to 50:50 over 20 column volumes and then hold for 5 column volumes) gave the title compound (75 mg, 34%) as a yellow solid: 1H NMR (500 MHz, CDCl3) δ 7.60 (d, J=9.0 Hz, 2H), 7.53 (d, J=8.0 Hz, 1H), 7.46 (d, J=7.5 Hz, 1H), 7.37 (d, J=1.5 Hz, 1H), 7.08 (d, J=7.5 Hz, 1H), 7.00 (d, J=9.0 Hz, 2H), 6.86 (d, J=2.0 Hz, 1H), 6.50 (dd, J=7.0, 2.0 Hz, 1H), 4.66-4.64 (m, 2H), 3.87 (s, 3H), 3.85-3.84 (m, 2H), 3.64 (s, 3H), 2.84-2.83 (m, 2H), 1.50 (s, 9H).

Workup

  1. customdegassed under vacuum for 15 min
  2. additionwere added
  3. customThe degassing/Ar flushing process
  4. temperatureThe suspension was cooled
  5. additiondiluted with 20% NH4OH/MeOH (25 mL)
  6. additionThe suspension was further diluted with CH2Cl2 (100 mL)
  7. filtrationThe solution was filtered through silica gel
  8. concentrationconcentrated under reduced pressure
  9. additionThe concentrate was diluted with CH2Cl2
  10. washwashed with brine (3×25 mL)
  11. dry with materialThe organic phase was dried over Na2SO4
  12. filtrationfiltered
  13. concentrationconcentrated to dryness
  14. temperatureFlash column chromatography (12 g ISCO column, (1:1 hexanes/EtOAc)/(80:18:2 CH2Cl2/MeOH/NH4OH), 100:0 for 10 column volumes, increased to 50:50 over 20 column volumes

Sources & evidence

ORD record
ord-4adea5cadb3e4e9a9bfccb80425c7eb5
Source dataset
uspto-grants-2016_03
Patent number
US09296743B2

Reaction notes

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