Bromine → HCID 22318054, compound

HRID 497063Notes

Reaction equation

HRID 497063 reaction equation
[ClH:1].[NH2:2][C:3]1[S:4][CH:5]=[C:6]([C:8]2[CH:13]=[CH:12][C:11]([NH:14][C:15]([CH2:17][N:18]([C:28]3[CH:33]=[CH:32][C:31]([F:34])=[CH:30][CH:29]=3)[C:19](=[O:27])[C:20]3[CH:25]=[CH:24][C:23]([F:26])=[CH:22][CH:21]=3)=[O:16])=[CH:10][CH:9]=2)[N:7]=1.[Br:35]Br>C(O)(=O)C.O>[ClH:1].[NH2:2][C:3]1[S:4][C:5]([Br:35])=[C:6]([C:8]2[CH:9]=[CH:10][C:11]([NH:14][C:15]([CH2:17][N:18]([C:28]3[CH:29]=[CH:30][C:31]([F:34])=[CH:32][CH:33]=3)[C:19](=[O:27])[C:20]3[CH:25]=[CH:24][C:23]([F:26])=[CH:22][CH:21]=3)=[O:16])=[CH:12][CH:13]=2)[N:7]=1

Participants

5

Reactant 2

HCID 24408BromineHCID 22318105HCID 22318105, compound

Product 1

HCID 22318054HCID 22318054, compound

Reagents, catalysts & solvents 2

HCID 176Acetic AcidSolventHCID 962WaterSolvent

Procedure

N-{[4-(2-aminothiazol-4-yl)phenylcarbamoyl]methyl}-4-fluoro-N-(4-fluorophenyl)benzamide monohydrochloride (200 mg) was dissolved in a mixed solvent of acetic acid (10 ml) and water (5 ml), mixed with bromine (20 μl) under ice-cooling and then stirred at room temperature for 5 minutes. The reaction solution was concentrated under a reduced pressure, and the residue was dissolved in ethyl acetate (30 ml)-saturated sodium bicarbonate aqueous solution (20 ml). The organic layer was washed with saturated brine, dried with anhydrous sodium sulfate and then concentrated under a reduced pressure. The residue was dissolved in ethyl acetate (5 ml) and mixed with 4 M hydrogen chloride in ethyl acetate solution (0.15 ml), and the thus precipitated solid was collected by filtration, dried and then recrystallized from methanol-ether, thereby obtaining 184 mg of N-{[4-(2-amino-5-bromothiazol-4-yl)phenylcarbamoyl]methyl}-4-fluoro-N-(4-fluorophenyl)benzamide monohydrochloride (colorless powder).

Workup

  1. temperaturecooling
  2. concentrationThe reaction solution was concentrated under a reduced pressure
  3. dissolutionthe residue was dissolved in ethyl acetate (30 ml)-saturated sodium bicarbonate aqueous solution (20 ml)
  4. washThe organic layer was washed with saturated brine
  5. dry with materialdried with anhydrous sodium sulfate
  6. concentrationconcentrated under a reduced pressure
  7. dissolutionThe residue was dissolved in ethyl acetate (5 ml)
  8. additionmixed with 4 M hydrogen chloride in ethyl acetate solution (0.15 ml)
  9. filtrationthe thus precipitated solid was collected by filtration
  10. customdried
  11. customrecrystallized from methanol-ether

Sources & evidence

ORD record
ord-3131de2ac09d425e91a8c541036434be
Source dataset
uspto-grants-2005_09
Patent number
US06949543B2

Reaction notes

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