3-Bromothiophene → Methyl 3-bromo-1-(thiophen-3-yl)-1H-indazole-6-carboxylate

HRID 1047636Notes

Reaction equation

HRID 1047636 reaction equation
[Br:1][C:2]1[C:10]2[C:5](=[CH:6][C:7]([C:11]([O:13][CH3:14])=[O:12])=[CH:8][CH:9]=2)[NH:4][N:3]=1.Br[C:16]1[CH:20]=[CH:19][S:18][CH:17]=1.CN[C@@H]1CCCC[C@H]1NC.[O-]P([O-])([O-])=O.[K+].[K+].[K+]>C1(C)C=CC=CC=1.[Cu]I>[Br:1][C:2]1[C:10]2[C:5](=[CH:6][C:7]([C:11]([O:13][CH3:14])=[O:12])=[CH:8][CH:9]=2)[N:4]([C:16]2[CH:20]=[CH:19][S:18][CH:17]=2)[N:3]=1

Participants

7

Reactant 4

HCID 133833-BromothiopheneHCID 62657Potassium Phosphate, TribasicHCID 2733821trans-N,N'-dimethyl-1,2-cyclohexanediamineHCID 178497093methyl 3-bromo-1H-indazole-6-carboxylate

Product 1

HCID 66661365Methyl 3-bromo-1-(thiophen-3-yl)-1H-indazole-6-carboxylateYield 59.5%

Reagents, catalysts & solvents 2

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 1140TolueneSolvent

Conditions

Temperature
120 °C

Procedure

Methyl 3-bromo-1H-indazole-6-carboxylate (1.801 g, 7.06 mmol), 3-bromothiophene (2.00 mL, 21.35 mmol), trans-1,2-bis(methylamino)cyclohexane (233 μL, 1.478 mmol), copper(I) iodide (142.8 mg, 0.750 mmol), and potassium phosphate tribasic (3.10 g, 14.60 mmol) were dissolved in toluene (35 ml) in a sealed tube and heated to 120° C. The reaction was allowed to stir for 3 h. The reaction was stopped, cooled to room temperature, quenched by addition of saturated aqueous ammonium chloride (25 mL), and the mixture extracted with ethyl acetate (3×30 mL). The combined organic phases were washed with saturated aqueous sodium chloride (1×20 mL), dried (sodium sulfate), filtered, and the solvent evaporated under reduced pressure. The crude product was purified by flash chromatography (RediSep SiO2, 120 g column) on a CombiFlash Rf purification system eluting with ethyl acetate-hexanes (0-35%). The title compound (1.4177 g, 4.20 mmol, 59.5% yield) was recovered as a white solid. LC-MS: [M+1]=337.0.

Workup

  1. temperaturecooled to room temperature
  2. customquenched by addition of saturated aqueous ammonium chloride (25 mL)
  3. extractionthe mixture extracted with ethyl acetate (3×30 mL)
  4. washThe combined organic phases were washed with saturated aqueous sodium chloride (1×20 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, 120 g column) on a CombiFlash Rf purification system
  9. washeluting with ethyl acetate-hexanes (0-35%)

Sources & evidence

ORD record
ord-8523dd37c3004e388d3495fd3168648b
Source dataset
uspto-grants-2013_10
Patent number
US08569512B2

Reaction notes

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