8-Hydroxyquinoline → N-Benzyl-4-methyl-2-(2-oxo-1-phenyl-1,2-dihydropyridine-4-carboxamido)thiazole-5-carboxamide

HRID 45385

Reaction equation

HRID 45385 reaction equation
[CH2:1]([NH:8][C:9]([C:11]1[S:15][C:14]([NH:16][C:17]([C:19]2[CH:24]=[CH:23][NH:22][C:21](=[O:25])[CH:20]=2)=[O:18])=[N:13][C:12]=1[CH3:26])=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C(=O)([O-])[O-].[K+].[K+].O[C:34]1[CH:35]=[CH:36][CH:37]=[C:38]2[C:43]=1N=CC=C2.IC1C=CC=CC=1>CS(C)=O.[Cu]I>[CH2:1]([NH:8][C:9]([C:11]1[S:15][C:14]([NH:16][C:17]([C:19]2[CH:24]=[CH:23][N:22]([C:34]3[CH:35]=[CH:36][CH:37]=[CH:38][CH:43]=3)[C:21](=[O:25])[CH:20]=2)=[O:18])=[N:13][C:12]=1[CH3:26])=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

7

Reactant 4

HCID 19238-HydroxyquinolineHCID 11430Potassium CarbonateHCID 11575IodobenzeneHCID 59369671N-Benzyl-4-methyl-2-(2-oxo-1,2-dihydropyridine-4-carboxamido)thiazole-5-carboxamide

Product 1

HCID 59369687N-Benzyl-4-methyl-2-(2-oxo-1-phenyl-1,2-dihydropyridine-4-carboxamido)thiazole-5-carboxamideYield 20%

Reagents, catalysts & solvents 2

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

Conditions

Temperature
130 °C

Procedure

To a degassed solution of N-benzyl-4-methyl-2-(2-oxo-1,2-dihydropyridine-4-carboxamido)thiazole-5-carboxamide (0.060 g, 0.16 mmol), potassium carbonate (0.033 g, 0.24 mmol) and 8-hydroxyquinoline (0.0034 g, 0.024 mmol) in dimethyl sulfoxide (5 mL) were added iodobenzene (0.039 g, 0.19 mmol) and finally copper(I) iodide (0.0046 g, 0.025 mmol). The reaction mixture was heated at 130° C. for 16 hours, then cooled to ambient temperature and filtered. The solvent was removed in vacuo. The residue was dissolved in dichloromethane (40 mL) and washed with saturated aqueous sodium bicarbonate solution (2×20 mL), and brine (20 mL). The organic layer was dried over anhydrous sodium sulfate, filtered, and the filtrate was concentrate in vacuo. The residue was recrystallized from ethyl acetate and methanol to yield a colorless solid in 20% yield (0.012 g); m.p. 260-262° C.; 1H NMR (DMSO-d6, 300 MHz) δ 13.11 (s, br., 1H), 8.63 (t, J=5.8 Hz, 1H), 7.78 (d, J=7.1 Hz, 1H), 7.58-7.37 (m, 5H), 7.35-7.26 (m, 4H), 7.23-7.18 (m, 1H), 7.14 (d, J=1.5 Hz, 1H), 6.75 (dd, J=1.5, 7.1 Hz, 1H), 4.38 (d, J=5.8 Hz, 2H), 2.51 (s, 3H); 13C NMR (DMSO-d6, 75 MHz) δ 165.5, 162.0, 162.0, 161.3, 140.7, 140.2, 140.0, 139.9, 137.9, 129.6, 128.9, 128.7, 127.7, 127.2, 127.0, 120.9, 103.7, 43.1, 16.9; MS (ES+) m/z 445.0 (M+1).

Workup

  1. temperaturecooled to ambient temperature
  2. filtrationfiltered
  3. customThe solvent was removed in vacuo
  4. dissolutionThe residue was dissolved in dichloromethane (40 mL)
  5. washwashed with saturated aqueous sodium bicarbonate solution (2×20 mL), and brine (20 mL)
  6. dry with materialThe organic layer was dried over anhydrous sodium sulfate
  7. filtrationfiltered
  8. concentrationthe filtrate was concentrate in vacuo
  9. customThe residue was recrystallized from ethyl acetate and methanol
  10. customto yield a colorless solid in 20% yield (0.012 g)

Sources & evidence

ORD record
ord-7326c1c8797b4bc1946991714a7757f9
Source dataset
uspto-grants-2013_09
Patent number
US08541457B2

Linked notes

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