Methyl iodide → HCID 178469302, compound

HRID 1880416Notes

Reaction equation

HRID 1880416 reaction equation
[OH:1][C:2]1[CH:3]=[C:4]([C:12]([O:14][CH2:15][CH3:16])=[O:13])[CH:5]=[C:6]2[C:10]=1[NH:9][N:8]=[C:7]2[CH3:11].[H-].[Na+].I[CH3:20]>CN(C=O)C.CCOC(C)=O.C([O-])(O)=O.[Na+].O.[Na+].[Cl-]>[CH3:20][O:1][C:2]1[CH:3]=[C:4]([C:12]([O:14][CH2:15][CH3:16])=[O:13])[CH:5]=[C:6]2[C:10]=1[NH:9][N:8]=[C:7]2[CH3:11]

Participants

9

Reactant 3

HCID 6328Methyl iodideHCID 24758Sodium hydrideHCID 178469296HCID 178469296, compound

Product 1

HCID 178469302HCID 178469302, compoundYield 33%

Reagents, catalysts & solvents 5

HCID 962WaterSolventHCID 5234Sodium ChlorideSolventHCID 6228DimethylformamideSolvent2×HCID 8857Ethyl AcetateSolventHCID 516892Sodium BicarbonateSolvent

Procedure

To a solution of ethyl 7-hydroxy-3-methyl-1H-indazole-5-carboxylate (Anti-Cancer Drug Design 1997, 12, 555) in DMF (25 mL) at 0° C. was added 60% oil dispersion of NaH (152 mg, 3.81 mmol). The mixture was stirred for 1 hour before the dropwise addition of a solution of iodomethane (0.54 g, 0.24 mL, 3.8 mmol) in DMF (3 mL). The mixture was kept at 0° C. for several hours before allowing the mixture to warm to room temperature and stirred overnight. The reaction was diluted with EtOAc, saturated aqueous NaHCO3, water and saturated aqueous NaCl. The organic extract was dried over Na2SO4, filtered and concentrated. The material was purified by silica gel chromatography (80 g column) eluting with a 0-30% EtOAc/hexanes gradient to provide ethyl 7-methoxy-3-methyl-1H-indazole-5-carboxylate (294 mg, 33%).

Workup

  1. waitThe mixture was kept at 0° C. for several hours
  2. extractionThe organic extract
  3. dry with materialwas dried over Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe material was purified by silica gel chromatography (80 g column)
  7. washeluting with a 0-30% EtOAc/hexanes gradient

Sources & evidence

ORD record
ord-51ea1df1922e4e7c985ed47592779579
Source dataset
uspto-grants-2012_11
Patent number
US08318762B2

Reaction notes

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