Sulfuric Acid → 4-(3-bromo-4-fluorophenyl)-7-ethyl-7H-imidazo[4,5-c]pyridazine

HRID 1846004Notes

Reaction equation

HRID 1846004 reaction equation
S(=O)(=O)(O)O.[CH2:6]([N:8]1[C:12]2[N:13]=[N:14][CH:15]=[C:16]([C:17]3[CH:22]=[CH:21][C:20]([F:23])=[CH:19][CH:18]=3)[C:11]=2[N:10]=[CH:9]1)[CH3:7].[Br:24]N1C(C)(C)C(=O)N(Br)C1=O.S(=O)(O)[O-].[Na+].[OH-].[Na+]>CCOC(C)=O>[Br:24][C:19]1[CH:18]=[C:17]([C:16]2[C:11]3[N:10]=[CH:9][N:8]([CH2:6][CH3:7])[C:12]=3[N:13]=[N:14][CH:15]=2)[CH:22]=[CH:21][C:20]=1[F:23]

Participants

7

Reactant 5

HCID 1118Sulfuric AcidHCID 64791,3-Dibromo-5,5-dimethylhydantoinHCID 14798Sodium HydroxideHCID 23665763Sodium BisulfiteHCID 867232317-Ethyl-4-(4-fluorophenyl)-7H-imidazo[4,5-c]pyridazine

Product 1

HCID 867232324-(3-bromo-4-fluorophenyl)-7-ethyl-7H-imidazo[4,5-c]pyridazineYield 41%

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Procedure

Concentrated sulphuric acid (66 g, 0.67 mol) was carefully added to 7-ethyl-4-(4-fluorophenyl)-7H-imidazo[4,5-c]pyridazine (Preparation 9, 2.3 g, 9.5 mmol) surrounded by an ice bath, and the resultant reaction mixture was gently stirred at room temperature until a homogeneous solution was observed. To this solution was added 1,3-dibromo-5,5-dimethylhydantoin (2.7 g, 9.5 mmol) portion-wise, and stirring was continued at 0° C. for 2 hours. The reaction mixture was poured carefully into aqueous sodium bisulphite (200 mL), and then basified with an aqueous sodium hydroxide solution (2 M) to pH=8 keeping the temperature below 20° C. EtOAc (50 mL) was added and the layers were separated. The aqueous layer was extracted with EtOAc (2×50 mL). The combined organic phases were washed with saturated brine solution, dried over Na2SO4 and concentrated in vacuo. The residue was purified by silica gel column chromatography eluting with petroleum ether:CH2Cl2 1:1 followed by trituration with EtOAc to afford the title compound as a white solid in 41% yield, 1.25 g.

Workup

  1. customsurrounded by an ice bath
  2. customthe resultant reaction mixture
  3. stirringstirring
  4. customthe temperature below 20° C
  5. customthe layers were separated
  6. extractionThe aqueous layer was extracted with EtOAc (2×50 mL)
  7. washThe combined organic phases were washed with saturated brine solution
  8. dry with materialdried over Na2SO4
  9. concentrationconcentrated in vacuo
  10. customThe residue was purified by silica gel column chromatography
  11. washeluting with petroleum ether:CH2Cl2 1:1

Sources & evidence

ORD record
ord-72b51c8a849f4579a44e7005e8ab029b
Source dataset
uspto-grants-2015_02
Patent number
US08952008B2

Reaction notes

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