4-Bromotoluene → Methyl 1-(4-methylphenyl)-1H-indazole-6-carboxylate

HRID 1047622Notes

Reaction equation

HRID 1047622 reaction equation
[NH:1]1[C:9]2[C:4](=[CH:5][CH:6]=[C:7]([C:10]([O:12][CH3:13])=[O:11])[CH:8]=2)[CH:3]=[N:2]1.Br[C:15]1[CH:20]=[CH:19][C:18]([CH3:21])=[CH:17][CH:16]=1.P([O-])([O-])([O-])=O.[K+].[K+].[K+].CN[C@H]1[C@H](NC)CCCC1.IC1C=CC(C)=CC=1>C1(C)C=CC=CC=1.[Cu](I)I>[CH3:21][C:18]1[CH:19]=[CH:20][C:15]([N:1]2[C:9]3[C:4](=[CH:5][CH:6]=[C:7]([C:10]([O:12][CH3:13])=[O:11])[CH:8]=3)[CH:3]=[N:2]2)=[CH:16][CH:17]=1

Participants

8

Reactant 5

HCID 78054-BromotolueneHCID 122074-IodotolueneHCID 62657Potassium Phosphate, TribasicHCID 286535methyl 1H-indazole-6-carboxylateHCID 2733821trans-N,N'-dimethyl-1,2-cyclohexanediamine

Product 1

HCID 66661292Methyl 1-(4-methylphenyl)-1H-indazole-6-carboxylateYield 58%

Reagents, catalysts & solvents 2

HCID 83717Copper iodideCatalystHCID 1140TolueneSolvent

Conditions

Temperature
120 °C

Procedure

To a solution of methyl 1H-indazole-6-carboxylate (2.0 g, 11.4 mmol) in toluene (11.4 mL) was added 4-bromotoluene (2.33 g, 13.6 mmol), tribasic potassium phophate (4.8 g, 22.7 mmol), copper iodide (0.12 g, 0.60 mmol) and trans-(1R,2R)—N,N′-bismethyl-1,2-cyclohexanediamine (0.18 mL, 1.14 mmol). The reaction mixture was stirred in a sealed tube at 120° C. After 10 min, 4-iodotoluene (3.01 g) was added and the mixture was stirred at 120° C. for another 2 h. The mixture was cooled to ambient temperature and quenched with saturated sodium bicarbonate (20 mL). The mixture was extracted with ethyl acetate (3×20 mL). The combined organic layers were washed with saturated aqueous sodium chloride (1×15 mL), dried over sodium sulfate, filtered and concentrated under reduced pressure to give the title compound (1.76 g): LC-MS [M+1]=267.1.

Workup

  1. stirringthe mixture was stirred at 120° C. for another 2 h
  2. temperatureThe mixture was cooled to ambient temperature
  3. customquenched with saturated sodium bicarbonate (20 mL)
  4. extractionThe mixture was extracted with ethyl acetate (3×20 mL)
  5. washThe combined organic layers were washed with saturated aqueous sodium chloride (1×15 mL)
  6. dry with materialdried over sodium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-eaa5887286204ca68a061d13f4f31759
Source dataset
uspto-grants-2013_10
Patent number
US08569512B2

Reaction notes

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