Isopropyl iodide → Methyl 6-bromo-3-formyl-1-isopropyl-1H-indazole-4-carboxylate

HRID 85480Notes

Reaction equation

HRID 85480 reaction equation
[Br:1][C:2]1[CH:3]=[C:4]([C:13]([O:15][CH3:16])=[O:14])[C:5]2[C:6]([CH:11]=[O:12])=[N:7][NH:8][C:9]=2[CH:10]=1.C([O-])([O-])=O.[K+].[K+].I[CH:24]([CH3:26])[CH3:25]>CN(C=O)C.O>[Br:1][C:2]1[CH:3]=[C:4]([C:13]([O:15][CH3:16])=[O:14])[C:5]2[C:6]([CH:11]=[O:12])=[N:7][N:8]([CH:24]([CH3:26])[CH3:25])[C:9]=2[CH:10]=1

Participants

6

Reactant 3

HCID 6362Isopropyl iodideHCID 11430Potassium CarbonateHCID 178497028HCID 178497028, compound

Product 1

HCID 71742648Methyl 6-bromo-3-formyl-1-isopropyl-1H-indazole-4-carboxylate

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

To a stirred solution of methyl 6-bromo-3-formyl-1H-indazole-4-carboxylate 1 (11.5 g, 40.63 mmol) in DMF (230 mL)) was added K2CO3 (14.08 g, 102.02 mmol) at RT under argon, and stirred for 10 min. Then 2-iodopropane (7.24 g, 42.58 mmol) was added at RT and the mixture stirred at 40° C. for 2 h. The reaction mixture was diluted with cold water and extracted with ethyl acetate (4×300 mL). The combined organic layers were washed with water, brine, dried over anhydrous Na2SO4, filtered, and concentrated. The crude residue (12.4 g) was purified by silica gel chromatography (eluent: 0-10% ethyl acetate: pet ether) to afford the title compound as an off white solid (5.55 g, 42%). 1H NMR (CDCl3, 400 MHz): δ 1.659 (d, J=6.4 Hz, 6H), 4.017 (s, 3H), 4.862-4.960 (m, 1H), 7.807 (s, 1H), 7.854 (s, 1H), 10.375 (s, 1H). HPLC: 98.66%.

Workup

  1. stirringthe mixture stirred at 40° C. for 2 h
  2. extractionextracted with ethyl acetate (4×300 mL)
  3. washThe combined organic layers were washed with water, brine
  4. dry with materialdried over anhydrous Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe crude residue (12.4 g) was purified by silica gel chromatography (eluent: 0-10% ethyl acetate: pet ether)

Sources & evidence

ORD record
ord-bed8b3597309468483d1553451c55f1c
Source dataset
uspto-grants-2014_09
Patent number
US08846935B2

Reaction notes

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