Isopropyl iodide → 4-iodo-1-isopropyl-1H-indazole-6-carboxylic acid methyl ester

HRID 59807Notes

Reaction equation

HRID 59807 reaction equation
[CH3:1][O:2][C:3]([C:5]1[CH:13]=[C:12]2[C:8]([CH:9]=[N:10][NH:11]2)=[C:7]([I:14])[CH:6]=1)=[O:4].C([O-])([O-])=O.[Cs+].[Cs+].I[CH:22]([CH3:24])[CH3:23]>CN(C=O)C>[CH3:1][O:2][C:3]([C:5]1[CH:13]=[C:12]2[C:8]([CH:9]=[N:10][N:11]2[CH:22]([CH3:24])[CH3:23])=[C:7]([I:14])[CH:6]=1)=[O:4].[CH3:1][O:2][C:3]([C:5]1[CH:6]=[C:7]([I:14])[C:8]2[C:12]([CH:13]=1)=[N:11][N:10]([CH:22]([CH3:24])[CH3:23])[CH:9]=2)=[O:4]

Participants

6

Reactant 3

HCID 6362Isopropyl iodideHCID 10796Cesium carbonateHCID 24728119Methyl 4-iodo-1H-indazole-6-carboxylate

Product 2

HCID 596277684-iodo-1-isopropyl-1H-indazole-6-carboxylic acid methyl esterYield 50%HCID 675132094-iodo-2-isopropyl-2H-indazole-6-carboxylic acid methyl esterYield 32%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of 4-iodo-1H-indazole-6-carboxylic acid methyl ester (2.0 g, 6.62 mmol) in DMF (50 mL) was added Cs2CO3 (4.32 g, 13.24 mmol) followed by 2-iodopropane (0.5 mL, 7.94 mmol). The reaction mixture was stirred overnight at room temperature, then partitioned between water and ethyl acetate. The organic layer was separated, dried over MgSO4, filtered and concentrated under reduced pressure. The residue was purified by column chromatography to provide 1.13 g (50%) of 4-iodo-1-isopropyl-1H-indazole-6-carboxylic acid methyl ester (0.73 g (32%) of the regioisomer 4-iodo-2-isopropyl-2H-indazole-6-carboxylic acid methyl ester was also recovered).

Workup

  1. custompartitioned between water and ethyl acetate
  2. customThe organic layer was separated
  3. dry with materialdried over MgSO4
  4. filtrationfiltered
  5. concentrationconcentrated under reduced pressure
  6. customThe residue was purified by column chromatography

Sources & evidence

ORD record
ord-0e985fe88d9f432ca1fcfd7f409edafb
Source dataset
uspto-grants-2016_09
Patent number
US09440956B2

Reaction notes

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