Potassium Carbonate → HCID 57785936, compound

HRID 1398996Notes

Reaction equation

HRID 1398996 reaction equation
[Br:1][C:2]1[CH:7]=[CH:6][C:5]([NH:8][C:9]2[N:13]([CH2:14][CH2:15][CH2:16][CH2:17]O)[C:12]3[C:19]([CH:24]([CH2:27][CH3:28])[CH2:25][CH3:26])=[CH:20][CH:21]=[C:22]([Cl:23])[C:11]=3[N:10]=2)=[C:4]([O:29][C:30]([F:33])([F:32])[F:31])[CH:3]=1.CS(Cl)(=O)=O.S([O-])(=O)(=O)C.C(=O)([O-])[O-].[K+].[K+]>O1CCCC1.C(N(CC)CC)C.C(=O)([O-])O.[Na+].CN(C)C=O.O>[Br:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[C:9]3=[N:10][C:11]4[C:22]([Cl:23])=[CH:21][CH:20]=[C:19]([CH:24]([CH2:25][CH3:26])[CH2:27][CH3:28])[C:12]=4[N:13]3[CH2:14][CH2:15][CH2:16][CH2:17]2)=[C:4]([O:29][C:30]([F:33])([F:31])[F:32])[CH:3]=1

Participants

10

Reactant 4

HCID 11430Potassium CarbonateHCID 31297Methanesulfonyl chlorideHCID 85257MethanesulfonateHCID 68766466HCID 68766466, compound

Product 1

HCID 57785936HCID 57785936, compoundYield 49%

Reagents, catalysts & solvents 5

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolventHCID 8471TriethylamineSolventHCID 516892Sodium BicarbonateSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of 4-[2-{[4-bromo-2-(trifluoromethoxy)phenyl]amino}-4-chloro-7-(1-ethylpropyl)-1H-benzimidazol-1-yl]butan-1-ol (Reference Example 62; 1.63 g, 2.97 mmol) in tetrahydrofuran (40 mL) and triethylamine (2.0 mL) was added methanesulfonyl chloride (0.69 mL, 11.9 mmol) at 0° C. The mixture was stirred at 0° C. for 4 hr, diluted with aqueous sodium hydrogen carbonate and extracted with ethyl acetate. The combined organic layer was washed with brine, dried over anhydrous magnesium sulfate, filtered, and concentrated in vacuo. A mixture of the resulting mesylate, potassium carbonate (2.04 g, 14.8 mmol) in N,N-dimethylformamide (15 mL) was stirred at 70° C. for 3 hr. The mixture was diluted with water, and extracted with ethyl acetate. The combined organic layer was washed with brine, dried over anhydrous magnesium sulfate, filtered, and concentrated in vacuo. The residue was purified by flash column chromatography on silica gel eluting with a 0-30% ethyl acetate/n-hexane gradient mixture. The filtrate was concentrated in vacuo to give the solid, which was washed with n-hexane to give the title compound as a colorless powder (770 mg, 1.45 mmol, 49%).

Workup

  1. extractionextracted with ethyl acetate
  2. washThe combined organic layer was washed with brine
  3. dry with materialdried over anhydrous magnesium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. stirringwas stirred at 70° C. for 3 hr
  7. extractionextracted with ethyl acetate
  8. washThe combined organic layer was washed with brine
  9. dry with materialdried over anhydrous magnesium sulfate
  10. filtrationfiltered
  11. concentrationconcentrated in vacuo
  12. customThe residue was purified by flash column chromatography on silica gel eluting with a 0-30% ethyl acetate/n-hexane gradient mixture
  13. concentrationThe filtrate was concentrated in vacuo
  14. customto give the solid, which
  15. washwas washed with n-hexane

Sources & evidence

ORD record
ord-8e62053cad864976a4acafdf031a5684
Source dataset
uspto-grants-2014_12
Patent number
US08901141B2

Reaction notes

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