Potassium Carbonate → HCID 57786120, compound

HRID 1399231Notes

Reaction equation

HRID 1399231 reaction equation
[Cl:1][C:2]1[C:10]2[N:9]=[C:8]([NH:11][C:12]3[C:13]([CH3:18])=[N:14][O:15][C:16]=3[CH3:17])[N:7]([CH2:19][CH2:20][CH2:21][CH2:22]O)[C:6]=2[C:5]([CH:24]([CH2:27][CH3:28])[CH2:25][CH3:26])=[CH:4][CH:3]=1.CS(Cl)(=O)=O.C(=O)(O)[O-].[Na+].C(=O)([O-])[O-].[K+].[K+]>N1C=CC=CC=1.C(OCC)(=O)C>[Cl:1][C:2]1[C:10]2[N:9]=[C:8]3[N:11]([C:12]4[C:13]([CH3:18])=[N:14][O:15][C:16]=4[CH3:17])[CH2:22][CH2:21][CH2:20][CH2:19][N:7]3[C:6]=2[C:5]([CH:24]([CH2:27][CH3:28])[CH2:25][CH3:26])=[CH:4][CH:3]=1

Participants

7

Reactant 4

HCID 11430Potassium CarbonateHCID 31297Methanesulfonyl chlorideHCID 516892Sodium BicarbonateHCID 68773849HCID 68773849, compound

Product 1

HCID 57786120HCID 57786120, compoundYield 56.1%

Reagents, catalysts & solvents 2

HCID 1049PyridineSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of 4-{4-chloro-2-[(3,5-dimethylisoxazol-4-yl)amino]-7-(1-ethylpropyl)-1H-benzimidazol-1-yl}butan-1-ol (173 mg, 0.428 mmol) in pyridine (2 mL) was added methanesulfonyl chloride (0.10 mL, 1.28 mmol) dropwise at 0° C. The mixture was warmed to room temperature and stirred for 3 hr. Aqueous sodium bicarbonate was added and the mixture was extracted with ethyl acetate. Organic layer was washed with brine, dried over anhydrous sodium sulfate and concentrated in vacuo. The crude mesylate was dissolved in 1-methyl-2-pyrrolidinone (2 mL) and potassium carbonate (160 mg, 1.16 mmol) was added. The mixture was stirred at 80° C. for 3 hr. After cooling, the mixture was diluted with ethyl acetate, washed with water and brine, dried over anhydrous sodium sulfate and concentrated in vacuo. The residue was purified by flash chromatography on silica gel eluting with a 20-40% ethyl acetate/n-hexane gradient mixture followed by recrystallization from ethyl acetate/n-hexane to give the title compound (93 mg, 0.24 mmol, 56%) as a colorless solid.

Workup

  1. extractionthe mixture was extracted with ethyl acetate
  2. washOrganic layer was washed with brine
  3. dry with materialdried over anhydrous sodium sulfate
  4. concentrationconcentrated in vacuo
  5. dissolutionThe crude mesylate was dissolved in 1-methyl-2-pyrrolidinone (2 mL)
  6. stirringThe mixture was stirred at 80° C. for 3 hr
  7. temperatureAfter cooling
  8. washwashed with water and brine
  9. dry with materialdried over anhydrous sodium sulfate
  10. concentrationconcentrated in vacuo
  11. customThe residue was purified by flash chromatography on silica gel eluting with a 20-40% ethyl acetate/n-hexane gradient mixture
  12. customfollowed by recrystallization from ethyl acetate/n-hexane

Sources & evidence

ORD record
ord-04d80671b8c34cf8983e77a6cced3327
Source dataset
uspto-grants-2014_12
Patent number
US08901141B2

Reaction notes

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