8-Hydroxyquinoline → HCID 57950466, compound

HRID 930753Notes

Reaction equation

HRID 930753 reaction equation
[N:1]1[CH:2]=[CH:3][N:4]2[CH:9]=[C:8]([CH2:10][O:11][C:12]3[CH:17]=[CH:16][NH:15][C:14](=[O:18])[CH:13]=3)[CH:7]=[CH:6][C:5]=12.Br[C:20]1[CH:21]=[CH:22][C:23]2[C:24]3[CH2:33][N:32]([C:34]([O:36][C:37]([CH3:40])([CH3:39])[CH3:38])=[O:35])[CH2:31][CH2:30][C:25]=3[N:26]([CH3:29])[C:27]=2[CH:28]=1.OC1C=CC=C2C=1N=CC=C2.C([O-])([O-])=O.[Cs+].[Cs+]>CS(C)=O.[Cu]I>[N:1]1[CH:2]=[CH:3][N:4]2[CH:9]=[C:8]([CH2:10][O:11][C:12]3[CH:17]=[CH:16][N:15]([C:20]4[CH:21]=[CH:22][C:23]5[C:24]6[CH2:33][N:32]([C:34]([O:36][C:37]([CH3:40])([CH3:39])[CH3:38])=[O:35])[CH2:31][CH2:30][C:25]=6[N:26]([CH3:29])[C:27]=5[CH:28]=4)[C:14](=[O:18])[CH:13]=3)[CH:7]=[CH:6][C:5]=12

Participants

7

Reactant 4

HCID 19238-HydroxyquinolineHCID 10796Cesium carbonateHCID 57950375tert-Butyl 7-bromo-5-methyl-3,4-dihydro-1H-pyrido[4,3-b]indole-2(5H)-carboxylateHCID 57950447HCID 57950447, compound

Product 1

HCID 57950466HCID 57950466, compoundYield 28.4%

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-(imidazo[1,2-a]pyridin-6-ylmethoxy)pyridin-2(1H)-one (270 mg, 1.12 mmol), tert-butyl 7-bromo-5-methyl-3,4-dihydro-1H-pyrido[4,3-b]indole-2(5H)-carboxylate (493 mg, 1.35 mmol), CuI (257 mg, 1.35 mmol), 8-hydroxyquinoline (98 mg, 0.67 mmol) and Cs2CO3 (401 mg, 1.23 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 for 4.5 h. The suspension was cooled, 40:9:1 CH2Cl2/MeOH/NH4OH (50 mL) 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 concentrate under reduced pressure. Flash chromatography (silica gel, (1:1 EtOAc/hexanes)/(4:0.9:0.1 CH2Cl2/MeOH/NH4OH), 100:0 to 0:100) yielded the title compound (167 mg, 28%) as a yellow solid: 1H NMR (300 MHz, CDCl3) δ 8.34-8.25 (m, 1H), 7.79-7.61 (m, 3H), 7.58-7.50 (m, 1H), 7.40-7.25 (m, 3H), 7.07-6.69 (m, 1H), 6.17-6.10 (m, 1H), 6.09-6.02 (m, 1H), 5.11 (s, 2H), 4.65 (br s, 2H), 3.92-3.80 (m, 2H), 3.65 (s, 3H), 2.89-2.80 (m, 2H), 1.52 (s, 9H); ESI MS m/z 526 [M+H]+.

Workup

  1. customwas degassed under reduced pressure for 45 min
  2. temperatureThe suspension was cooled
  3. addition40:9:1 CH2Cl2/MeOH/NH4OH (50 mL) 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. concentrationconcentrate under reduced pressure

Sources & evidence

ORD record
ord-34df8cc70b784df6b4922227c805ca63
Source dataset
uspto-grants-2016_03
Patent number
US09296743B2

Reaction notes

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