Potassium Carbonate → HCID 57786129, compound

HRID 1398998Notes

Reaction equation

HRID 1398998 reaction equation
[Cl:1][C:2]1[C:10]2[N:9]=[C:8]([NH:11][C:12]3[C:13]([O:18][CH3:19])=[N:14][CH:15]=[CH:16][CH:17]=3)[N:7]([CH2:20][CH2:21][CH2:22][CH2:23]O)[C:6]=2[C:5]([CH:25]([CH2:28][CH3:29])[CH2:26][CH3:27])=[CH:4][CH:3]=1.CS(Cl)(=O)=O.C(=O)([O-])[O-].[K+].[K+]>N1C=CC=CC=1.CN(C)C=O.O>[Cl:1][C:2]1[C:10]2[N:9]=[C:8]3[N:11]([C:12]4[C:13]([O:18][CH3:19])=[N:14][CH:15]=[CH:16][CH:17]=4)[CH2:23][CH2:22][CH2:21][CH2:20][N:7]3[C:6]=2[C:5]([CH:25]([CH2:28][CH3:29])[CH2:26][CH3:27])=[CH:4][CH:3]=1

Participants

7

Reactant 3

HCID 11430Potassium CarbonateHCID 31297Methanesulfonyl chlorideHCID 68763066HCID 68763066, compound

Product 1

HCID 57786129HCID 57786129, compoundYield 71.6%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 1049PyridineSolventHCID 6228DimethylformamideSolvent

Procedure

To a solution of 4-{4-chloro-7-(1-ethylpropyl)-2-[(2-methoxypyridin-3-yl)amino]-1H-benzimidazol-1-yl}butan-1-ol (200 mg, 0.480 mmol) in pyridine (5 mL) was added methanesulfonyl chloride (275 mg, 2.40 mmol) at 0° C. The mixture was stirred at room temperature for 1 hr. The reaction mixture was concentrated in vacuo. The residue was dissolved in water and ethyl acetate. The mixture was extracted with ethyl acetate (×2). The organics were dried over magnesium sulfate, filtered, and concentrated in vacuo. The resulting crude mesylate (MS Calcd.: 398; Found: 399 (M+H)) was subjected for the next step without further purification. The crude material in N,N-dimethylformamide (3.0 mL) was added potassium carbonate (663 mg, 4.80 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 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 to give the title compound (137 mg, 0.343 mmol, 71.6% yield) as a white amorphous.

Workup

  1. concentrationThe reaction mixture was concentrated in vacuo
  2. dissolutionThe residue was dissolved in water
  3. extractionThe mixture was extracted with ethyl acetate (×2)
  4. dry with materialThe organics were dried over magnesium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customThe resulting crude mesylate (MS Calcd.: 398; Found: 399 (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. dry with materialThe combined organic layer was dried over anhydrous magnesium sulfate
  12. filtrationfiltered
  13. concentrationconcentrated in vacuo
  14. customThe residue was purified by silica gel column chromatography
  15. washeluting with a 0-20% ethyl acetate/n-hexane gradient mixture

Sources & evidence

ORD record
ord-9a2aebdafae646a8a3e96cd81de0c6b0
Source dataset
uspto-grants-2014_12
Patent number
US08901141B2

Reaction notes

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