Methyl iodide → 8-Bromo-1-(1,3-dimethyl-1H-pyrazol-4-yl)-3-methyl-1,3-dihydro-imidazo[4,5-c]quinolin-2-one

HRID 445536

Reaction equation

HRID 445536 reaction equation
[OH-].[Na+].[Br:3][C:4]1[CH:13]=[CH:12][C:11]2[N:10]=[CH:9][C:8]3[NH:14][C:15](=[O:24])[N:16]([C:17]4[C:18]([CH3:23])=[N:19][N:20]([CH3:22])[CH:21]=4)[C:7]=3[C:6]=2[CH:5]=1.I[CH3:26]>[Br-].C([N+](CCCC)(CCCC)CCCC)CCC.C(Cl)Cl.O>[Br:3][C:4]1[CH:13]=[CH:12][C:11]2[N:10]=[CH:9][C:8]3[N:14]([CH3:26])[C:15](=[O:24])[N:16]([C:17]4[C:18]([CH3:23])=[N:19][N:20]([CH3:22])[CH:21]=4)[C:7]=3[C:6]=2[CH:5]=1

Participants

7

Reactant 3

HCID 6328Methyl iodide2×HCID 14798Sodium HydroxideHCID 596198918-bromo-1-(1,3-dimethyl-1H-pyrazol-4-yl)-1,3-dihydro-imidazo[4,5-c]quinolin-2-one

Product 1

HCID 596197398-Bromo-1-(1,3-dimethyl-1H-pyrazol-4-yl)-3-methyl-1,3-dihydro-imidazo[4,5-c]quinolin-2-one

Reagents, catalysts & solvents 3

HCID 74236Tetrabutylammonium BromideCatalystHCID 962WaterSolventHCID 6344DichloromethaneSolvent

Procedure

NaOH (0.568 g, 14.19 mmol) and tetrabutylammonium bromide (0.229 g, 0.710 mmol) were added to a mixture of 8-bromo-1-(1,3-dimethyl-1H-pyrazol-4-yl)-1,3-dihydro-imidazo[4,5-c]quinolin-2-one (Stage A.1, 3.10 g, 7.100 mmol) in DCM (108 ml) and H2O (54 ml) and stirred at rt for 5 min. Then iodomethane (1.52 ml, 24.1 mmol) was added and the mixture was stirred for 14 h at rt. Iodomethane (0.4 ml, 6.35 mmol) was added and the RM was stirred at rt for 23.5 h. Then the RM was extracted with DCM (2×), washed with saturated aqueous NaHCO3 and brine, dried over Na2SO4, filtered and evaporated to dryness. The residue was dissolved in DCM and purified by flash chromatography (DCM/MeOH 0%-4.5%) to give the title compound as a brownish solid (HPLC: tR 2.37 min (Method A); M+H=374 MS-ES; 1H-NMR (d6-DMSO, 400 MHz) 9.00 (s, 1H), 8.08 (s, 1H), 7.91-7.99 (m, 1H), 7.64-7.71 (m, 1H), 7.41-7.47 (m, 1H), 3.90 (s, 3H), 3.55 (s, 3H), 1.94 (s, 3H))

Workup

  1. stirringthe mixture was stirred for 14 h at rt
  2. stirringthe RM was stirred at rt for 23.5 h
  3. extractionThen the RM was extracted with DCM (2×)
  4. washwashed with saturated aqueous NaHCO3 and brine
  5. dry with materialdried over Na2SO4
  6. filtrationfiltered
  7. customevaporated to dryness
  8. dissolutionThe residue was dissolved in DCM
  9. custompurified by flash chromatography (DCM/MeOH 0%-4.5%)

Sources & evidence

ORD record
ord-e76b909bf85349afb60cae6ab88cb06e
Source dataset
uspto-grants-2013_07
Patent number
US08476294B2

Linked notes

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