Toluene → HCID 178478944, compound

HRID 1825918Notes

Reaction equation

HRID 1825918 reaction equation
[Cl:1][C:2]1[C:3]([NH:7][C:8]2[NH:12][C:11]3[CH:13]=[CH:14][C:15]([F:17])=[CH:16][C:10]=3[N:9]=2)=[CH:4][S:5][CH:6]=1.[Br:18]N1C(=O)CCC1=O.C1(C)C=CC=CC=1>C(O)(=O)C>[ClH:1].[Br:18][C:4]1[S:5][CH:6]=[C:2]([Cl:1])[C:3]=1[NH:7][C:8]1[NH:12][C:11]2[CH:13]=[CH:14][C:15]([F:17])=[CH:16][C:10]=2[N:9]=1

Participants

5

Reactant 3

HCID 1140TolueneHCID 67184N-bromobutanimideHCID 178505472HCID 178505472, compound

Product 1

HCID 178478944HCID 178478944, compound

Reagents, catalysts & solvents 1

HCID 176Acetic AcidSolvent2×

Procedure

(4-Chloro-thiophen-3-yl)-(5-fluoro-1H-benzoimidazol-2-yl)-amine (50 mg, example 54b) was dissolved in acetic acid (4 ml) and at room temperature with vigorous stirring N-bromosuccinimide (33 mg) dissolved in acetic acid (4 ml) was slowly added. After stirring for 45 min at room temperature toluene (20 ml) was added and the solvent mixture distilled off. The residue was dissolved in ethyl acetate and washed with saturated potassium carbonate solution. The organic layer was dried (MgSO4), filtered and concentrated. The residue was purified by preparative HPLC, the product containing fractions were combined, the acetonitrile was removed, the aqueous residue set basic and three times extracted with ethyl acetate. The organic layers were combined, dried (MgSO4) and filtered. After removal of the solvent water and 2 N HCl were added to the residue. After freeze drying the desired product (27 mg) was obtained.

Workup

  1. additionwas slowly added
  2. additionwas added
  3. distillationthe solvent mixture distilled off
  4. dissolutionThe residue was dissolved in ethyl acetate
  5. washwashed with saturated potassium carbonate solution
  6. dry with materialThe organic layer was dried (MgSO4)
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customThe residue was purified by preparative HPLC
  10. additionthe product containing fractions
  11. customthe acetonitrile was removed
  12. extractionthree times extracted with ethyl acetate
  13. dry with materialdried (MgSO4)
  14. filtrationfiltered
  15. customAfter removal of the solvent water and 2 N HCl
  16. additionwere added to the residue
  17. dry with materialAfter freeze drying the desired product (27 mg)
  18. customwas obtained

Sources & evidence

ORD record
ord-6b85182fec1d4ff680240126d6165e48
Source dataset
uspto-grants-2006_05
Patent number
US07049333B2

Reaction notes

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