Methyl iodide → Methyl 1-methyl-1H-indazole-5-carboxylate

HRID 1880389Notes

Reaction equation

HRID 1880389 reaction equation
[NH:1]1[C:9]2[C:4](=[CH:5][C:6]([C:10]([O:12][CH3:13])=[O:11])=[CH:7][CH:8]=2)[CH:3]=[N:2]1.[C:14]([O-])([O-])=O.[K+].[K+].IC>CN(C=O)C>[CH3:14][N:1]1[C:9]2[C:4](=[CH:5][C:6]([C:10]([O:12][CH3:13])=[O:11])=[CH:7][CH:8]=2)[CH:3]=[N:2]1.[CH3:14][N:2]1[CH:3]=[C:4]2[C:9]([CH:8]=[CH:7][C:6]([C:10]([O:12][CH3:13])=[O:11])=[CH:5]2)=[N:1]1

Participants

6

Reactant 3

HCID 6328Methyl iodideHCID 11430Potassium CarbonateHCID 22260640Methyl 1H-indazole-5-carboxylate

Product 2

HCID 37818676Methyl 1-methyl-1H-indazole-5-carboxylateYield 40%HCID 37818686Methyl 2-methyl-2H-indazole-5-carboxylateYield 8.4%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of methyl 1H-indazole-5-carboxylate (2.5 g, 14 mmol) in DMF (45 mL) was added K2CO3 (4.90 g, 35.5 mmol) followed by iodomethane (1.77 mL, 28.4 mmol). The mixture was stirred at room temperature for 2 hours and then heated at 50° C. overnight. The mixture was concentrated, dissolved in EtOAc and washed with saturated aqueous NaCl. The organic extract was dried over Na2SO4, filtered and concentrated. The crude material was purified by CombiFlash (80 g column, 25-45% EtOAc/heptane) to provide methyl 1-methyl-1H-indazole-5-carboxylate (1.07 g, 40%) and methyl 2-methyl-2H-indazole-5-carboxylate (227 mg, 8.4%).

Workup

  1. temperatureheated at 50° C. overnight
  2. concentrationThe mixture was concentrated
  3. dissolutiondissolved in EtOAc
  4. washwashed with saturated aqueous NaCl
  5. extractionThe organic extract
  6. dry with materialwas dried over Na2SO4
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customThe crude material was purified by CombiFlash (80 g column, 25-45% EtOAc/heptane)

Sources & evidence

ORD record
ord-7f05cfa9830944b8a963202eacfa62bf
Source dataset
uspto-grants-2012_11
Patent number
US08318762B2

Reaction notes

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