8-Hydroxyquinoline → HCID 57950327, compound

HRID 1020667Notes

Reaction equation

HRID 1020667 reaction equation
[CH2:1]([O:8][C:9]1[CH:14]=[CH:13][NH:12][C:11](=[O:15])[CH:10]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=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])[C:27]([CH3:39])([CH3:38])[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>[CH2:1]([O:8][C:9]1[CH:14]=[CH:13][N:12]([C:17]2[CH:25]=[C:24]3[C:20]([C:21]4[CH2:30][CH2:29][N:28]([C:31]([O:33][C:34]([CH3:37])([CH3:36])[CH3:35])=[O:32])[C:27]([CH3:39])([CH3:38])[C:22]=4[N:23]3[CH3:26])=[CH:19][CH:18]=2)[C:11](=[O:15])[CH:10]=1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

7

Reactant 4

HCID 19238-HydroxyquinolineHCID 10796Cesium carbonateHCID 36077244-Benzyloxy-2(1H)-pyridoneHCID 57950257HCID 57950257, compound

Product 1

HCID 57950327HCID 57950327, compoundYield 27.1%

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-(benzyloxy)pyridin-2(1H)-one (107 mg, 0.532 mmol), tert-butyl 7-bromo-1,1,9-trimethyl-3,4-dihydro-1H-pyrido[3,4-b]indole-2(9H)-carboxylate (251 mg, 0.639 mmol), CuI (122 mg, 0.639 mmol), 8-hydroxyquinoline (93 mg, 0.639 mmol) and Cs2CO3 (190 mg, 0.585 mmol) in DMSO (10 mL) was degassed under reduced pressure for 45 min. The suspension was put under Ar and heated at 135° C. with stirring overnight. The suspension was cooled, 40:9:1 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 solution was dried over Na2SO4 and concentrated under reduced pressure to afford an amorphous solid. Flash chromatography (silica gel, (1:1 EtOAc/hexanes)/(9:0.9:0.1 CH2Cl2/MeOH/NH4OH) 100:0 to 1:1) yielded the title compound (74 mg, 27%) as a white powder: 1H NMR (300 MHz, CDCl3) δ 7.54 (d, J=8.1 Hz, 1H), 7.46-7.35 (m, 4H), 7.33-7.25 (m, 3H), 7.12 (dd, J=8.1, 2.1 Hz, 1H), 6.09 (d, J=2.6 Hz, 1H), 6.04 (dd, J=7.5, 2.6 Hz, 1H), 5.06 (s, 2H), 3.80 (s, 3H), 3.77 (t, J=4.8 Hz, 2H), 2.77 (t, J=4.8 Hz, 2H), 1.89 (s, 6H), 1.54 (s, 9H).

Workup

  1. customwas degassed under reduced pressure for 45 min
  2. temperatureThe suspension was cooled
  3. addition40:9:1 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 solution was dried over Na2SO4
  7. concentrationconcentrated under reduced pressure
  8. customto afford an amorphous solid

Sources & evidence

ORD record
ord-355d4fe3ff544d41b91fb39fd909c5d8
Source dataset
uspto-grants-2014_05
Patent number
US08716308B2

Reaction notes

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