1-Bromo-2-methylpropane → 1-Isobutyl-5-methoxy-1H-indazole

HRID 909225Notes

Reaction equation

HRID 909225 reaction equation
[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:9](=[CH:10][CH:11]=1)[NH:8][N:7]=[CH:6]2.C([O-])([O-])=O.[K+].[K+].Br[CH2:19][CH:20]([CH3:22])[CH3:21]>CN(C=O)C>[CH2:19]([N:8]1[C:9]2[C:5](=[CH:4][C:3]([O:2][CH3:1])=[CH:11][CH:10]=2)[CH:6]=[N:7]1)[CH:20]([CH3:22])[CH3:21]

Participants

5

Reactant 3

HCID 65551-Bromo-2-methylpropane2×HCID 11430Potassium CarbonateHCID 133468605-Methoxy-1H-indazole

Product 1

HCID 574187691-Isobutyl-5-methoxy-1H-indazoleYield 36.5%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A solution of 5-methoxy-1H-indazole (5.00 g, 33.7 mmol) in DMF (100 mL) was treated with K2CO3 (5.83 g, 42.2 mmol) and stirred at room temperature for 15 minutes. To this solution was added 1-bromo-2-methylpropane (5.09 g, 37.1 mmol) and the resulting mixture was heated to 110° C. for 18 hours. Another equivalent of 1-bromo-2-methyl-propane was added and the mixture continued to heat for 48 hours more. The mixture was concentrated under reduced pressure and dissolved in dichloromethane. The solution was washed with 1N HCl, filtered, and concentrated under reduced pressure. The residue was chromatographed on Biotage eluting with hexanes/ether (5:1) to afford 2.51 g of orange oil (36% yield).

Workup

  1. temperaturethe resulting mixture was heated to 110° C. for 18 hours
  2. temperatureto heat for 48 hours more
  3. concentrationThe mixture was concentrated under reduced pressure
  4. dissolutiondissolved in dichloromethane
  5. washThe solution was washed with 1N HCl
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure
  8. customThe residue was chromatographed on Biotage
  9. washeluting with hexanes/ether (5:1)

Sources & evidence

ORD record
ord-f454034d95eb45a5b94538c28779b71f
Source dataset
uspto-grants-2011_09
Patent number
US08017641B2

Reaction notes

Loading…