Sodium hydride → HCID 21082053, compound

HRID 347013Notes

Reaction equation

HRID 347013 reaction equation
[H-].[Na+].[Cl:3][C:4]1[CH:5]=[C:6]([C:10]2[C:19]3[C:14](=[CH:15][CH:16]=[C:17]([C:20]([C:28]4[CH:33]=[CH:32][C:31]([Cl:34])=[CH:30][CH:29]=4)([OH:27])[C:21]4[N:25]([CH3:26])[CH:24]=[N:23][N:22]=4)[CH:18]=3)[NH:13][C:12](=[O:35])[CH:11]=2)[CH:7]=[CH:8][CH:9]=1.Br[CH2:37][C:38]1[CH:45]=[CH:44][C:41]([C:42]#[N:43])=[CH:40][CH:39]=1>CN(C=O)C>[Cl:3][C:4]1[CH:5]=[C:6]([C:10]2[C:19]3[C:14](=[CH:15][CH:16]=[C:17]([C:20]([C:28]4[CH:29]=[CH:30][C:31]([Cl:34])=[CH:32][CH:33]=4)([OH:27])[C:21]4[N:25]([CH3:26])[CH:24]=[N:23][N:22]=4)[CH:18]=3)[N:13]([CH2:37][C:38]3[CH:45]=[CH:44][C:41]([C:42]#[N:43])=[CH:40][CH:39]=3)[C:12](=[O:35])[CH:11]=2)[CH:7]=[CH:8][CH:9]=1

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 869964-(Bromomethyl)benzonitrileHCID 21082041HCID 21082041, compound

Product 1

HCID 21082053HCID 21082053, compoundYield 6.3%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

NaH 60% in oil (0.0023 mol) was added at room temperature to a mixture of 4-(3-chlorophenyl)-6-[(4-chlorophenyl)hydroxy(4-methyl-4H-1,2,4-triazol-3-yl)methyl]-2(1H)-quinolinone (0.0021 mol), obtained in Example B32, in DMF (10 ml). The mixture was stirred for 30 minutes. 4-(Bromomethyl)-benzonitrile (0.0023 mol) was added. The mixture was stirred at room temperature for 18 hours, then at 80° C. for 2 hours, then overnight, cooled and poured out into ice water. The precipitate was filtered, taken up in DCM. The organic layer was separated, dried (MgSO4), filtered, and the solvent was evaporated. The residue (0.8 g) was purified by column chromatography over silica gel (eluent: CH2Cl2/CH3OH 100/0 to 90/10; 10 μm). The pure fractions were collected and the solvent was evaporated. The residue (0.1 g) was purified by column chromatography over kromasil (eluent: CH3CN/H2O 60/40; 10 μm). The pure fractions were collected and the solvent was evaporated, yielding 0.078 g (6%) of 4-[[4-(3-chlorophenyl)-6-[(4-chlorophenyl)hydroxy(4-methyl-4H-1,2,4-triazol-3-yl)methyl]-2-oxo-1(2H)-quinolinyl]methyl]-benzonitrile, mp. 185° C.

Workup

  1. stirringThe mixture was stirred at room temperature for 18 hours
  2. waitat 80° C. for 2 hours
  3. temperatureovernight, cooled
  4. filtrationThe precipitate was filtered
  5. customThe organic layer was separated
  6. dry with materialdried (MgSO4)
  7. filtrationfiltered
  8. customthe solvent was evaporated
  9. customThe residue (0.8 g) was purified by column chromatography over silica gel (eluent: CH2Cl2/CH3OH 100/0 to 90/10; 10 μm)
  10. customThe pure fractions were collected
  11. customthe solvent was evaporated
  12. customThe residue (0.1 g) was purified by column chromatography over kromasil (eluent: CH3CN/H2O 60/40; 10 μm)
  13. customThe pure fractions were collected
  14. customthe solvent was evaporated

Sources & evidence

ORD record
ord-8908eef05a99414d83d76de299092643
Source dataset
uspto-grants-2007_02
Patent number
US07173040B2

Reaction notes

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