Pyridine → HCID 68775643, compound

HRID 1628643Notes

Reaction equation

HRID 1628643 reaction equation
[Cl:1][C:2]1[C:10]2[N:9]=[C:8]([NH:11][C:12]3[C:17]([CH3:18])=[CH:16][C:15](Cl)=[CH:14][C:13]=3[O:20][CH3:21])[N:7]([CH:22](CC)[CH2:23]O)[C:6]=2[C:5]([CH:27]([CH2:30][CH3:31])[CH2:28][CH3:29])=[CH:4][CH:3]=1.CS(Cl)(=O)=O.[C:37](=O)([O-])[O-].[K+].[K+].N1C=CC=[CH:45][CH:44]=1>C(=O)([O-])O.[Na+].O>[Cl:1][C:2]1[C:10]2[N:9]=[C:8]3[N:11]([C:12]4[C:17]([CH3:18])=[CH:16][C:15]([CH3:37])=[CH:14][C:13]=4[O:20][CH3:21])[CH2:44][CH2:45][CH2:23][CH2:22][N:7]3[C:6]=2[C:5]([CH:27]([CH2:30][CH3:31])[CH2:28][CH3:29])=[CH:4][CH:3]=1

Participants

7

Reactant 4

HCID 1049PyridineHCID 11430Potassium CarbonateHCID 31297Methanesulfonyl chlorideHCID 68771245HCID 68771245, compound

Product 1

HCID 68775643HCID 68775643, compoundYield 40%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 516892Sodium BicarbonateSolvent

Procedure

To a solution of 2-{4-chloro-2-[(4-chloro-2-methoxy-6-methylphenyl)amino]-7-(1-ethylpropyl)-1H-benzimidazol-1-yl}butan-1-ol (60 mg, 0.129 mmol) in pyridine (0.5 mL) was added methanesulfonyl chloride (0.050 ml, 0.645 mmol) at 0° C., and the mixture was stirred at room temperature for 1 hr. The mixture was diluted with saturated aqueous sodium hydrogen carbonate at 0° C. and extracted with ethyl acetate. The extracts were washed with brine, dried over anhydrous magnesium sulfate and concentrated in vacuo. The resulting mesylate was dissolved in N,N-dimethylformamide (1 mL) and potassium carbonate (36 mg, 258 mmol) was added. The mixture was stirred at 80° C. for 15 hr. After cooling, the mixture was diluted with water and extracted with ethyl acetate. The extracts were washed with saturated aqueous sodium hydrogen carbonate and brine, dried over magnesium sulfate and concentrated in vacuo. The residue was purified by silica gel column chromatography eluting with a 1-15% ethyl acetate/n-hexane gradient mixture. The desired fractions were concentrated in vacuo, and the resulting solid was recrystallized from methanol to give the title compound (23 mg, 0.0515 mmol, 40%) as a colorless crystal.

Workup

  1. extractionextracted with ethyl acetate
  2. washThe extracts were washed with brine
  3. dry with materialdried over anhydrous magnesium sulfate
  4. concentrationconcentrated in vacuo
  5. dissolutionThe resulting mesylate was dissolved in N,N-dimethylformamide (1 mL)
  6. stirringThe mixture was stirred at 80° C. for 15 hr
  7. temperatureAfter cooling
  8. extractionextracted with ethyl acetate
  9. washThe extracts were washed with saturated aqueous sodium hydrogen carbonate and brine
  10. dry with materialdried over magnesium sulfate
  11. concentrationconcentrated in vacuo
  12. customThe residue was purified by silica gel column chromatography
  13. washeluting with a 1-15% ethyl acetate/n-hexane gradient mixture
  14. concentrationThe desired fractions were concentrated in vacuo
  15. customthe resulting solid was recrystallized from methanol

Sources & evidence

ORD record
ord-1716bf6377f3432aa0aaa399a4e6fb5b
Source dataset
uspto-grants-2014_07
Patent number
US08785460B2

Reaction notes

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