Methyl iodide → 4-(3-Chloro-phenyl)-6-[(6-chloro-pyridin-3-yl)-hydroxy-(3-methyl-3H-imidazol-4-yl)-methyl]-1-methyl-1H-quinolin-2-one

HRID 1936284Notes

Reaction equation

HRID 1936284 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([C:8]2[C:17]3[C:12](=[CH:13][CH:14]=[C:15]([C:18]([C:26]4[CH:27]=[N:28][C:29]([Cl:32])=[CH:30][CH:31]=4)([OH:25])[C:19]4[N:20]([CH3:24])[CH:21]=[N:22][CH:23]=4)[CH:16]=3)[NH:11][C:10](=[O:33])[CH:9]=2)[CH:5]=[CH:6][CH:7]=1.[OH-].[Na+].[CH3:36]I>C1COCC1.[Cl-].C([N+](CC)(CC)CC)C1C=CC=CC=1>[Cl:1][C:2]1[CH:3]=[C:4]([C:8]2[C:17]3[C:12](=[CH:13][CH:14]=[C:15]([C:18]([C:26]4[CH:27]=[N:28][C:29]([Cl:32])=[CH:30][CH:31]=4)([OH:25])[C:19]4[N:20]([CH3:24])[CH:21]=[N:22][CH:23]=4)[CH:16]=3)[N:11]([CH3:36])[C:10](=[O:33])[CH:9]=2)[CH:5]=[CH:6][CH:7]=1

Participants

6

Reactant 3

HCID 6328Methyl iodideHCID 14798Sodium HydroxideHCID 155378354-(3-chloro-phenyl)-6-[(6-chloro-pyridin-3-yl)-hydroxy-(3-methyl-3H-imidazol-4-yl)-methyl]-1H-quinolin-2-one

Product 1

HCID 111793634-(3-Chloro-phenyl)-6-[(6-chloro-pyridin-3-yl)-hydroxy-(3-methyl-3H-imidazol-4-yl)-methyl]-1-methyl-1H-quinolin-2-oneYield 55.4%

Reagents, catalysts & solvents 2

HCID 66133Benzyl triethylammonium chlorideCatalystHCID 8028TetrahydrofuranSolvent2×

Procedure

To a solution of 4-(3-chloro-phenyl)-6-[(6-chloro-pyridin-3-yl)-hydroxy-(3-methyl-3H-imidazol-4-yl)-methyl]-1H-quinolin-2-one (351 mg, 0.737 mmol) in THF (15 ml) was added a 40% aqueous NaOH (2 ml), benzyltriethylammonium chloride (84 mg, 0.369 mmol) and a solution of methyl iodide (0.078 ml, 1.25 mmol) in THF (4 ml). The reaction mixture was stirred at ambient temperature for 4 hours after which time it was partitioned between CHCl3 and water. The organic layer was washed with brine, dried over MgSO4 and concentrated under vacuum to give the crude product. It was chromatographed on silica gel with MeOH-CHCl3—NH4OH (2:98:0.2 to 5:95:0.5) as eluents to afford the title compound as a white solid (200.3 mg, 0.408 mmol, 55% yield).

Workup

  1. customwas partitioned between CHCl3 and water
  2. washThe organic layer was washed with brine
  3. dry with materialdried over MgSO4
  4. concentrationconcentrated under vacuum
  5. customto give the crude product
  6. customIt was chromatographed on silica gel with MeOH-CHCl3—NH4OH (2:98:0.2 to 5:95:0.5) as eluents

Sources & evidence

ORD record
ord-11619477edf145658dc818c1a94a9835
Source dataset
uspto-grants-2002_05
Patent number
US06388092B2

Reaction notes

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