8-Hydroxyquinoline → HCID 57950420, compound

HRID 930779Notes

Reaction equation

HRID 930779 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:20][CH2:19][C:18]2[C:17]3[C:12](=[CH:13][C:14](Br)=[CH:15][CH:16]=3)[N:11]([CH3:22])[C:10]=2[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[N:23]1[C:24]([CH2:32][O:33][C:34]2[CH:39]=[CH:38][NH:37][C:36](=[O:40])[CH:35]=2)=[CH:25][N:26]2[CH:31]=[CH:30][CH:29]=[CH:28][C:27]=12.C([O-])([O-])=O.[Cs+].[Cs+].OC1C=CC=C2C=1N=CC=C2>CS(C)=O.[Cu](I)I>[C:1]([O:5][C:6]([N:8]1[CH2:20][CH2:19][C:18]2[C:17]3[C:12](=[CH:13][C:14]([N:37]4[CH:38]=[CH:39][C:34]([O:33][CH2:32][C:24]5[N:23]=[C:27]6[CH:28]=[CH:29][CH:30]=[CH:31][N:26]6[CH:25]=5)=[CH:35][C:36]4=[O:40])=[CH:15][CH:16]=3)[N:11]([CH3:22])[C:10]=2[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

7

Reactant 4

HCID 19238-HydroxyquinolineHCID 10796Cesium carbonateHCID 57950386HCID 57950386, compoundHCID 57950468tert-butyl 7-bromo-9-methyl-1,3,4,9-tetrahydro-2H-pyrido[3,4-b]indole-2-carboxylate

Product 1

HCID 57950420HCID 57950420, compoundYield 40.3%

Reagents, catalysts & solvents 2

HCID 83717Copper iodideCatalystHCID 679Dimethyl SulfoxideSolvent

Conditions

Temperature
130 °C

Procedure

tert-Butyl-7-bromo-9-methyl-3,4-dihydro-1H-pyrido[3,4-b]indole-2(9H)-carboxylate (0.328 g, 0.898 mmol), 4-(imidazo[1,2-a]pyridin-2-ylmethoxy)pyridine-2(1H)-one (0.240 g, 0.998 mmol) and Cs2CO3 (0.358 g, 1.09 mmol) were suspended in DMSO (4.0 mL), and argon was bubbled through the system for 10 minutes. 8-Hydroxyquinoline (43.4 mg, 0.299 mmol) and copper iodide (228 mg, 1.20 mmol) were added, and resulting suspension was placed under vacuum for 15 min. The system was flushed with argon. The evacuation/argon flushing process was repeated a total of three times. The reaction mixture was heated at 130° C. for 18 h under argon. The mixture was cooled, and a solution of 20% NH4OH in MeOH (40 mL) was added. The resulting mixture was stirred for 1 h. The mixture was diluted with CH2Cl2 and filtered through a silica gel plug. The filtrate was collected and concentrated. The residue was diluted with CH2Cl2, washed with brine (3×25 mL), dried over Na2SO4 and concentrated under reduced pressure. Purification by flash column chromatography (80 g ISCO column, (1:1 hexanes/EtOAc)/(80:18:2 CH2Cl2/MeOH/NH4OH), 80:20 to 0:100:0 over 10 column volumes and then hold for 8 column volumes) gave the title compound (0.190 g, 40%) as a yellow foam: 1H NMR (500 MHz, DMSO-d6) δ 8.12 (d, J=6.8 Hz, 1H), 7.69 (s, 1H), 7.61 (d, J=9.1 Hz, 1H), 7.52 (d, J=8.3 Hz, 1H), 7.31-7.29 (m, 2H), 7.22-7.19 (m, 1H), 7.02 (dd, J=8.3, 1.7 Hz, 1H), 6.83-6.80 (m, 1H), 6.17 (d, J=2.7 Hz, 1H), 6.07 (dd, J=7.6, 2.7 Hz, 1H), 5.25 (s, 2H), 4.64 (m, 2H), 3.75 (m, 2H), 3.63 (s, 3H), 2.80 (m, 2H), 1.52 (s, 9H), ESI MS m/z 526 [M+H]+.

Workup

  1. customargon was bubbled through the system for 10 minutes
  2. customresulting suspension
  3. customThe system was flushed with argon
  4. temperatureThe mixture was cooled
  5. additiona solution of 20% NH4OH in MeOH (40 mL) was added
  6. additionThe mixture was diluted with CH2Cl2
  7. filtrationfiltered through a silica gel plug
  8. customThe filtrate was collected
  9. concentrationconcentrated
  10. additionThe residue was diluted with CH2Cl2
  11. washwashed with brine (3×25 mL)
  12. dry with materialdried over Na2SO4
  13. concentrationconcentrated under reduced pressure
  14. customPurification by flash column chromatography (80 g ISCO column

Sources & evidence

ORD record
ord-06852a3fe87c48ff8d9afd3480d89212
Source dataset
uspto-grants-2016_03
Patent number
US09296743B2

Reaction notes

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