8-Hydroxyquinoline → HCID 57950371, compound

HRID 930757Notes

Reaction equation

HRID 930757 reaction equation
[CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([C:9]2[CH:14]=[CH:13][NH:12][C:11](=[O:15])[CH:10]=2)=[CH:5][CH:4]=1.Br[C:17]1[CH:25]=[C:24]2[C:20]([C:21]3[CH2:30][CH2:29][N:28]([C:31]([O:33][C:34]([CH3:37])([CH3:36])[CH3:35])=[O:32])[CH2:27][C:22]=3[N:23]2[CH3:26])=[CH:19][CH:18]=1.OC1C=CC=C2C=1N=CC=C2.C([O-])([O-])=O.[Cs+].[Cs+]>CS(C)=O.[Cu]I>[CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([C:9]2[CH:14]=[CH:13][N:12]([C:17]3[CH:25]=[C:24]4[C:20]([C:21]5[CH2:30][CH2:29][N:28]([C:31]([O:33][C:34]([CH3:37])([CH3:36])[CH3:35])=[O:32])[CH2:27][C:22]=5[N:23]4[CH3:26])=[CH:19][CH:18]=3)[C:11](=[O:15])[CH:10]=2)=[CH:5][CH:4]=1

Participants

7

Reactant 4

HCID 19238-HydroxyquinolineHCID 10796Cesium carbonateHCID 109435304-(4-methoxyphenyl)pyridin-2(1H)-oneHCID 57950468tert-butyl 7-bromo-9-methyl-1,3,4,9-tetrahydro-2H-pyrido[3,4-b]indole-2-carboxylate

Product 1

HCID 57950371HCID 57950371, compoundYield 40%

Reagents, catalysts & solvents 2

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 679Dimethyl SulfoxideSolvent

Conditions

Temperature
135 °C

Procedure

A suspension of 4-(4-methoxyphenyl)pyridin-2(1H)-one (103 mg, 0.510 mmol), tert-butyl 7-bromo-9-methyl-3,4-dihydro-1H-pyrido[3,4-b]indole-2(9H)-carboxylate (223 mg, 0.612 mmol), CuI (116 mg, 0.612 mmol), 8-hydroxyquinoline (15 mg, 0.10 mmol) and Cs2CO3 (183 mg, 0.561 mmol) in DMSO (10 mL) was degassed under reduced pressure for 45 min. The suspension was put under Ar and stirred at 135° C. overnight. The suspension was cooled, 9:0.9:0.1 CH2Cl2/MeOH/NH4OH was added, and the resulting suspension was stirred at 25° C. for 30 min. The suspension was passed through a plug of silica gel, and the filtrate was washed with brine. The resulting solution was dried over Na2SO4 and concentrated under reduced pressure. Flash chromatography (silica gel, (1:1 EtOAc/hexanes)/(9:0.9:0.1 CH2Cl2/MeOH/NH4OH), 100:0 to 0:100) afforded the title compound (98 mg, 40%) as a yellow powder: 1H NMR (300 MHz, CDCl3) δ 7.64-7.53 (m, 3H), 7.46 (d, J=7.2 Hz, 1H), 7.36 (br s, 1H), 7.08 (dd, J=8.1, 1.5 Hz, 1H), 7.01 (d, J=8.7 Hz, 2H), 6.87 (d, J=1.8 Hz, 1H), 6.51 (dd, J=7.2, 1.8 Hz, 1H), 4.68-4.60 (m, 2H), 3.88 (s, 3H), 3.82-3.73 (m, 2H), 3.65 (s, 3H), 2.85-2.78 (m, 2H), 1.52 (s, 9H).

Workup

  1. customwas degassed under reduced pressure for 45 min
  2. temperatureThe suspension was cooled
  3. addition9:0.9:0.1 CH2Cl2/MeOH/NH4OH was added
  4. stirringthe resulting suspension was stirred at 25° C. for 30 min
  5. washthe filtrate was washed with brine
  6. dry with materialThe resulting solution was dried over Na2SO4
  7. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-71719dd06bb5481183d49afeacbc9be1
Source dataset
uspto-grants-2016_03
Patent number
US09296743B2

Reaction notes

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