Methyl iodide → (S)-2-sec-Butylamino-6-(methanesulfonyl-methylamino)-isonicotinic acid methyl ester

HRID 732426Notes

Reaction equation

HRID 732426 reaction equation
[H-].[Na+].[CH3:3][O:4][C:5](=[O:22])[C:6]1[CH:11]=[C:10]([NH:12][S:13]([CH3:16])(=[O:15])=[O:14])[N:9]=[C:8]([NH:17][C@H:18]([CH2:20][CH3:21])[CH3:19])[CH:7]=1.I[CH3:24]>CN(C=O)C>[CH3:3][O:4][C:5](=[O:22])[C:6]1[CH:11]=[C:10]([N:12]([S:13]([CH3:16])(=[O:15])=[O:14])[CH3:24])[N:9]=[C:8]([NH:17][C@H:18]([CH2:20][CH3:21])[CH3:19])[CH:7]=1

Participants

5

Reactant 3

HCID 6328Methyl iodideHCID 24758Sodium hydrideHCID 68814626(S)-2-sec-butylamino-6-methanesulfonylamino-isonicotinic acid methyl ester

Product 1

HCID 68814724(S)-2-sec-Butylamino-6-(methanesulfonyl-methylamino)-isonicotinic acid methyl esterYield 86%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

Add sodium hydride (47 mg, 1.18 mmol, 60% dispersion in mineral oil) to a solution of (S)-2-sec-butylamino-6-methanesulfonylamino-isonicotinic acid methyl ester (356 mg, 1.18 mmol) in DMF (5 mL) at 0° C. Stir for 10 min, add iodomethane (0.11 mL, 1.77 mmol) dropwise. Stir the mixture at room temperature for 2 h, cool and quench the reaction with an ammonium chloride solution. Extract the mixture with ethyl acetate (3×30 mL) and wash the combined extract with water, saturated aqueous sodium chloride, dry (magnesium sulfate), concentrate and purify (silica gel chromatography, eluting with 20:80 ethyl acetate:hexanes) to give the title compound (320 mg, 86%).

Workup

  1. stirringStir the mixture at room temperature for 2 h
  2. temperaturecool
  3. customquench
  4. customthe reaction with an ammonium chloride solution
  5. extractionExtract the mixture with ethyl acetate (3×30 mL)
  6. washwash the
  7. extractioncombined extract with water, saturated aqueous sodium chloride
  8. dry with materialdry (magnesium sulfate)
  9. concentrationconcentrate
  10. custompurify
  11. wash(silica gel chromatography, eluting with 20:80 ethyl acetate:hexanes)

Sources & evidence

ORD record
ord-c8375a30e80847a5a25e828eb1d6e76a
Source dataset
uspto-grants-2009_09
Patent number
US07585885B2

Reaction notes

Loading…