4-Iodotoluene → HCID 66661508, compound

HRID 1047642Notes

Reaction equation

HRID 1047642 reaction equation
[CH3:1][O:2][C:3]([C:5]1[CH:6]=[C:7]2[C:11](=[CH:12][CH:13]=1)[NH:10][N:9]=[CH:8]2)=[O:4].I[C:15]1[CH:20]=[CH:19][C:18]([CH3:21])=[CH:17][CH:16]=1.CN[C@@H]1CCCC[C@H]1NC.P([O-])([O-])([O-])=O.[K+].[K+].[K+]>C1(C)C=CC=CC=1.[Cu](I)I>[CH3:21][C:18]1[CH:19]=[CH:20][C:15]([N:10]2[C:11]3[C:7](=[CH:6][C:5]([C:3]([O:2][CH3:1])=[O:4])=[CH:13][CH:12]=3)[CH:8]=[N:9]2)=[CH:16][CH:17]=1

Participants

7

Reactant 4

HCID 122074-IodotolueneHCID 62657Potassium Phosphate, TribasicHCID 2733821trans-N,N'-dimethyl-1,2-cyclohexanediamineHCID 22260640Methyl 1H-indazole-5-carboxylate

Product 1

HCID 66661508HCID 66661508, compoundYield 72.4%

Reagents, catalysts & solvents 2

HCID 83717Copper iodideCatalystHCID 1140TolueneSolvent

Conditions

Temperature
120 °C

Procedure

5-(1H)indazole carboxylic acid methyl ester (302.1 mg, 1.715 mmol), 4-iodotoluene (457.2 mg, 2.097 mmol), copper iodide (17.4 mg, 0.091 mmol), trans-1,2-bis(methylamino)cyclohexane (275 μl, 0.348 mmol), and tribasic potassium phosphate (771.4 mg, 3.63 mmol) were dissolved in toluene (1700 μl) at 25° C. under Ar. The reaction mixture was warmed to 120° C. and allowed to stir for 14 h. The reaction was stopped, cooled to room temperature, quenched by addition of saturated aqueous ammonium chloride (10 mL), and extracted with ethyl acetate (3×10 mL). The combined organic phases were washed with saturated aqueous sodium chloride (1×10 mL), dried (sodium sulfate), filtered, and the solvent evaporated under reduced pressure. The crude product was purified by flash chromatography (RediSep SiO2, 40 g column) on a CombiFlash Rf purification system eluting with ethyl acetate-hexanes (0-65%). The title compound (330.5 mg, 1.241 mmol, 72.4% yield) was recovered as a light yellow/white solid. LC-MS: [M+1]=267.3.

Workup

  1. temperaturecooled to room temperature
  2. customquenched by addition of saturated aqueous ammonium chloride (10 mL)
  3. extractionextracted with ethyl acetate (3×10 mL)
  4. washThe combined organic phases were washed with saturated aqueous sodium chloride (1×10 mL)
  5. dry with materialdried (sodium sulfate)
  6. filtrationfiltered
  7. customthe solvent evaporated under reduced pressure
  8. customThe crude product was purified by flash chromatography (RediSep SiO2, 40 g column) on a CombiFlash Rf purification system
  9. washeluting with ethyl acetate-hexanes (0-65%)

Sources & evidence

ORD record
ord-bc4949844534495492174a4fc75dab49
Source dataset
uspto-grants-2013_10
Patent number
US08569512B2

Reaction notes

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