Potassium Carbonate → HCID 57786097, compound

HRID 1398984Notes

Reaction equation

HRID 1398984 reaction equation
[Cl:1][C:2]1[C:10]2[N:9]=[C:8]([NH:11][C:12]3[CH:13]=[N:14][C:15]([N:19]4[CH2:23][CH2:22][CH2:21][CH2:20]4)=[CH:16][C:17]=3[CH3:18])[N:7]([CH2:24][CH2:25][CH2:26][CH2:27]O)[C:6]=2[C:5]([CH:29]([CH2:32][CH3:33])[CH2:30][CH3:31])=[CH:4][CH:3]=1.CS(Cl)(=O)=O.C(=O)(O)[O-].[Na+].C(=O)([O-])[O-].[K+].[K+]>N1C=CC=CC=1.O>[Cl:1][C:2]1[C:10]2[N:9]=[C:8]3[N:11]([C:12]4[CH:13]=[N:14][C:15]([N:19]5[CH2:23][CH2:22][CH2:21][CH2:20]5)=[CH:16][C:17]=4[CH3:18])[CH2:27][CH2:26][CH2:25][CH2:24][N:7]3[C:6]=2[C:5]([CH:29]([CH2:32][CH3:33])[CH2:30][CH3:31])=[CH:4][CH:3]=1

Participants

7

Reactant 4

HCID 11430Potassium CarbonateHCID 31297Methanesulfonyl chlorideHCID 516892Sodium BicarbonateHCID 68772647HCID 68772647, compound

Product 1

HCID 57786097HCID 57786097, compoundYield 39%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 1049PyridineSolvent

Procedure

To a solution of 4-{4-chloro-7-(1-ethylpropyl)-2-[(4-methyl-6-pyrrolidin-1-ylpyridin-3-yl)amino]-1H-benzimidazol-1-yl}butan-1-ol (Reference Example 48; 400 mg, 0.85 mmol) in pyridine (5 mL) was added methanesulfonyl chloride (0.330 mL, 4.25 mmol) dropwise at 0° C. The mixture was warmed to room temperature and stirred for 8 hr. Aqueous sodium bicarbonate was added and the mixture was extracted with ethyl acetate. Organic layer was washed with brine, dried over sodium sulfate and concentrated in vacuo. The resulting crude mesylate was dissolved in N,N-dimethylformamide (10 mL) and potassium carbonate (586 mg, 4.25 mmol) was added. The mixture was stirred at 80° C. for 16 hr. Water was added and the mixture was extracted with ethyl acetate. Organic layer was washed with water and brine, dried over anhydrous magnesium sulfate and concentrated in vacuo. The residue was purified by flash chromatography on silica gel eluting with a 50-80% ethyl acetate/n-hexane gradient mixture. The filtrate was concentrated in vacuo to give a solid, which was recrystallized from ethyl acetate/n-hexane to give the title compound (150 mg, 0.331 mmol, 39%) 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 sodium sulfate
  4. concentrationconcentrated in vacuo
  5. dissolutionThe resulting crude mesylate was dissolved in N,N-dimethylformamide (10 mL)
  6. stirringThe mixture was stirred at 80° C. for 16 hr
  7. extractionthe mixture was extracted with ethyl acetate
  8. washOrganic layer was washed with water and brine
  9. dry with materialdried over anhydrous magnesium sulfate
  10. concentrationconcentrated in vacuo
  11. customThe residue was purified by flash chromatography on silica gel eluting with a 50-80% ethyl acetate/n-hexane gradient mixture
  12. concentrationThe filtrate was concentrated in vacuo
  13. customto give a solid, which
  14. customwas recrystallized from ethyl acetate/n-hexane

Sources & evidence

ORD record
ord-cf3f0c14a7804d7f93731de6970f16b2
Source dataset
uspto-grants-2014_12
Patent number
US08901141B2

Reaction notes

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