Sodium hydride → 6-Chloro-3-[2-(3-chloro-2,6-difluoro-phenyl)-imidazol-1-ylmethyl]-4-methoxy-pyridazine

HRID 1244250Notes

Reaction equation

HRID 1244250 reaction equation
[Cl:1][C:2]1[N:7]=[N:6][C:5]([CH2:8]Cl)=[C:4]([O:10][CH3:11])[CH:3]=1.[Cl:12][C:13]1[C:14]([F:25])=[C:15]([C:20]2[NH:21][CH:22]=[CH:23][N:24]=2)[C:16]([F:19])=[CH:17][CH:18]=1.[H-].[Na+]>CN(C=O)C>[Cl:1][C:2]1[N:7]=[N:6][C:5]([CH2:8][N:21]2[CH:22]=[CH:23][N:24]=[C:20]2[C:15]2[C:16]([F:19])=[CH:17][CH:18]=[C:13]([Cl:12])[C:14]=2[F:25])=[C:4]([O:10][CH3:11])[CH:3]=1

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 219192722-(3-Chloro-2,6-difluoro-phenyl)-imidazoleHCID 219192946-Chloro-3-chloromethyl-4-methoxypyridazine

Product 1

HCID 103845636-Chloro-3-[2-(3-chloro-2,6-difluoro-phenyl)-imidazol-1-ylmethyl]-4-methoxy-pyridazine

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a stirred solution of 6-chloro-3-chloromethyl-4-methoxy-pyridazine (58 mg, 0.3 mmol) and 2-(3-chloro-2,6-difluoro-phenyl)-imidazole (65 mg, 0.3 mmol) in DMF (6 mL) is added NaH (60% suspension in mineral oil, 14 mg). The mixture is stirred at room temperature overnight. The solvent is removed in vacuo and water (5 mL) and EtOAc (8 mL) is added. The layers are separated and the aqueous layer is extracted with EtOAc (8 mL). The combined extracts is washed with brine (8 mL) and dried (Na2SO4) and evaporated. Preparative TLC purification (5% MeOH in CH2Cl2) of the residue provides the title compound as a light yellow oil. H1 NMR δ (CDCl3) 7.48–7.56 (m, 1H), 7.15–7.20 (m, 2H), 7.02 (t, 1H, J=8.4 Hz), 6.87 (s, 1H), 5.27 (s, 2H), 3.764 (s, 3H).

Workup

  1. customThe solvent is removed in vacuo and water (5 mL) and EtOAc (8 mL)
  2. additionis added
  3. customThe layers are separated
  4. extractionthe aqueous layer is extracted with EtOAc (8 mL)
  5. washThe combined extracts is washed with brine (8 mL)
  6. dry with materialdried (Na2SO4)
  7. customevaporated
  8. customPreparative TLC purification (5% MeOH in CH2Cl2) of the residue

Sources & evidence

ORD record
ord-15e6ad9fde974ebd85447e5a0f7082be
Source dataset
uspto-grants-2006_10
Patent number
US07122546B2

Reaction notes

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