Potassium Carbonate → HCID 57786324, compound

HRID 1628631Notes

Reaction equation

HRID 1628631 reaction equation
[Br:1][C:2]1[CH:7]=[C:6]([C:8]([F:11])([F:10])[F:9])[CH:5]=[CH:4][C:3]=1[NH:12][C:13]1[N:17]([CH2:18][CH2:19][CH2:20][CH2:21]O)[C:16]2[C:23]([CH:28]([CH2:31][CH3:32])[CH2:29][CH3:30])=[CH:24][CH:25]=[C:26]([Cl:27])[C:15]=2[N:14]=1.CS(Cl)(=O)=O.C(=O)([O-])[O-].[K+].[K+]>N1C=CC=CC=1.CN(C)C=O.O>[Br:1][C:2]1[CH:7]=[C:6]([C:8]([F:11])([F:10])[F:9])[CH:5]=[CH:4][C:3]=1[N:12]1[C:13]2=[N:14][C:15]3[C:26]([Cl:27])=[CH:25][CH:24]=[C:23]([CH:28]([CH2:31][CH3:32])[CH2:29][CH3:30])[C:16]=3[N:17]2[CH2:18][CH2:19][CH2:20][CH2:21]1

Participants

7

Reactant 3

HCID 11430Potassium CarbonateHCID 31297Methanesulfonyl chlorideHCID 68763481HCID 68763481, compound

Product 1

HCID 57786324HCID 57786324, compoundYield 863.4%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 1049PyridineSolventHCID 6228DimethylformamideSolvent

Procedure

To a solution of 4-[2-{[2-bromo-4-(trifluoromethyl)phenyl]amino}-4-chloro-7-(1-ethylpropyl)-1H-benzimidazol-1-yl]butan-1-ol (Reference Example 57; 109.2 mg, 0.205 mmol) in pyridine (0.5 mL) was added methanesulfonyl chloride (79.3 μL, 1.03 mmol) at 0° C. The reaction mixture was stirred at room temperature for 4 hr. The reaction mixture was quenched with aqueous sodium hydrogen carbonate and extracted with ethyl acetate (×3). The combined organic layer was washed with brine, dried over anhydrous magnesium sulfate, filtered and concentrated in vacuo. The resulting crude mesylate (MS Calcd.: 609; Found: 610 (M+H)) was subjected for the next step without further purification. To the crude material in N,N-dimethylformamide (1.0 mL) was added potassium carbonate (56.7 mg, 0.410 mmol). The reaction mixture was stirred at 80° C. for 4 hr. After cooling, the reaction mixture was diluted with water and extracted with ethyl acetate (×35) The combined organic layer was washed with water (×2) and brine, dried over anhydrous magnesium sulfate, filtered and concentrated in vacuo. The residue was purified by silica gel column chromatography eluting with a 0-20% ethyl acetate/n-hexane gradient mixture. The resulting solid was washed with n-hexane to give the title compound as a colorless powder (810.1 mg, 1.77 mmol, 71% (2 steps)).

Workup

  1. customThe reaction mixture was quenched with aqueous sodium hydrogen carbonate
  2. extractionextracted with ethyl acetate (×3)
  3. washThe combined organic layer was washed with brine
  4. dry with materialdried over anhydrous magnesium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customThe resulting crude mesylate (MS Calcd.: 609; Found: 610 (M+H)) was subjected for the next step without further purification
  8. stirringThe reaction mixture was stirred at 80° C. for 4 hr
  9. temperatureAfter cooling
  10. extractionextracted with ethyl acetate (×35) The combined organic layer
  11. washwas washed with water (×2) and brine
  12. dry with materialdried over anhydrous magnesium sulfate
  13. filtrationfiltered
  14. concentrationconcentrated in vacuo
  15. customThe residue was purified by silica gel column chromatography
  16. washeluting with a 0-20% ethyl acetate/n-hexane gradient mixture
  17. washThe resulting solid was washed with n-hexane

Sources & evidence

ORD record
ord-510c367fe48641c7ae51f2d47048c18a
Source dataset
uspto-grants-2014_07
Patent number
US08785460B2

Reaction notes

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