Potassium Carbonate → HCID 57786397, compound

HRID 1628628Notes

Reaction equation

HRID 1628628 reaction equation
[Br:1][C:2]1[CH:7]=[C:6]([CH3:8])[CH:5]=[CH:4][C:3]=1[NH:9][C:10]1[N:14]([CH2:15][CH2:16][CH2:17][CH2:18]O)[C:13]2[C:20]([CH:25]([CH2:28][CH3:29])[CH2:26][CH3:27])=[CH:21][CH:22]=[C:23]([Cl:24])[C:12]=2[N:11]=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]([CH3:8])[CH:5]=[CH:4][C:3]=1[N:9]1[C:10]2=[N:11][C:12]3[C:23]([Cl:24])=[CH:22][CH:21]=[C:20]([CH:25]([CH2:28][CH3:29])[CH2:26][CH3:27])[C:13]=3[N:14]2[CH2:15][CH2:16][CH2:17][CH2:18]1

Participants

7

Reactant 3

HCID 11430Potassium CarbonateHCID 31297Methanesulfonyl chlorideHCID 68761693HCID 68761693, compound

Product 1

HCID 57786397HCID 57786397, compoundYield 83.1%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 1049PyridineSolventHCID 6228DimethylformamideSolvent

Procedure

To a solution of 4-[2-[(2-bromo-4-methylphenyl)amino]-4-chloro-7-(1-ethylpropyl)-1H-benzimidazol-1-yl]butan-1-ol (Reference Example 54; 1.02 g, 2.13 mmol) in pyridine (2.5 mL) was added methanesulfonyl chloride (824 μL, 10.65 mmol) at 0° C. The reaction mixture was stirred at room temperature for 0.5 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 magnesium sulfate, filtered and concentrated in vacuo. The resulting crude mesylate (MS Calcd.: 555; Found: 556 (M+H)) was subjected for the next step without further purification. To the crude material in N,N-dimethylformamide (2.0 mL) was added potassium carbonate (588.8 mg, 4.26 mmol). The reaction mixture was stirred at 80° C. for 12 hr. After cooling, the reaction mixture was diluted with water and extracted with ethyl acetate (×3). 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, 83% (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 magnesium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customThe resulting crude mesylate (MS Calcd.: 555; Found: 556 (M+H)) was subjected for the next step without further purification
  8. stirringThe reaction mixture was stirred at 80° C. for 12 hr
  9. temperatureAfter cooling
  10. extractionextracted with ethyl acetate (×3)
  11. washThe combined organic layer was 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-e5a1b60767c54588b0efa2e1e1eafba4
Source dataset
uspto-grants-2014_07
Patent number
US08785460B2

Reaction notes

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