Dimethylformamide → HCID 66920633, compound

HRID 1880381Notes

Reaction equation

HRID 1880381 reaction equation
[CH2:1]([C:3]1[C:11]2[C:6](=[C:7]([OH:17])[CH:8]=[C:9]([C:12]([O:14][CH2:15][CH3:16])=[O:13])[CH:10]=2)[NH:5][N:4]=1)[CH3:2].[H-].[Na+].I[CH3:21].[CH3:22][N:23]([CH:25]=O)[CH3:24]>CCOC(C)=O.C([O-])(O)=O.[Na+]>[CH2:1]([C:3]1[C:11]2[C:6](=[C:7]([O:17][CH3:22])[CH:8]=[C:9]([C:12]([O-:14])=[O:13])[CH:10]=2)[NH:5][N:4]=1)[CH3:2].[CH2:1]([C:3]1[C:11]2[C:25](=[C:7]([O:17][CH3:21])[CH:8]=[C:9]([C:12]([O:14][CH2:15][CH3:16])=[O:13])[CH:10]=2)[N:23]([CH3:24])[N:4]=1)[CH3:2]

Participants

8

Reactant 4

HCID 6228DimethylformamideHCID 6328Methyl iodideHCID 24758Sodium hydrideHCID 178469297HCID 178469297, compound

Product 2

HCID 66920633HCID 66920633, compoundYield 60%HCID 178438018HCID 178438018, compoundYield 41%

Reagents, catalysts & solvents 2

HCID 8857Ethyl AcetateSolventHCID 516892Sodium BicarbonateSolvent

Procedure

To a 0° C. solution of ethyl 3-ethyl-7-hydroxy-1H-indazole-5-carboxylate (prepared as described in Acid Preparation 2) (50 mg, 0.21 mmol) in DMF (1 mL) was added 60% NaH oil dispersion (8.5 mg, 0.21 mmol). This mixture was stirred for 30 minutes before addition of iodomethane (0.011 mL, 0.17 mmol). The reaction was kept at 0° C. for 2 hours before allowing to alowly warm to room temperature while stirring overnight. The reaction was diluted with EtOAc and saturated aqueous NaHCO3. The organic phase was isolated and the aqueous phase was back extracted with EtOAc (2×). The combined organic extracts were washed with saturated aqueous NaCl, dried over Na2SO4, filtered and concentrated. The crude product was purified by CombiFlash (12 g column, 0-30% EtOAc/hexanes) to provide 3-ethyl-7-methoxy-1H-indazole-5-carboxylate (22 mg, 41%) and ethyl 3-ethyl-7-methoxy-1-methyl-1H-indazole-5-carboxylate (46 mg, 60%).

Workup

  1. customThe organic phase was isolated
  2. extractionthe aqueous phase was back extracted with EtOAc (2×)
  3. washThe combined organic extracts were washed with saturated aqueous NaCl
  4. dry with materialdried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe crude product was purified by CombiFlash (12 g column, 0-30% EtOAc/hexanes)

Sources & evidence

ORD record
ord-d626b8944636426db9e9e703137b0b17
Source dataset
uspto-grants-2012_11
Patent number
US08318762B2

Reaction notes

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