Diisopropylamine → Methyl 3-(prop-1-en-2-yl)-1-(thiophen-3-yl)-1H-indazole-6-carboxylate

HRID 1047637Notes

Reaction equation

HRID 1047637 reaction equation
Br[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:15]2[CH:19]=[CH:18][S:17][CH:16]=2)[N:3]=1.[C:20](B1OC(C)(C)C(C)(C)O1)([CH3:22])=[CH2:21].C(NC(C)C)(C)C>CN(C)C=O.O.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[CH2:21]=[C:20]([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:15]2[CH:19]=[CH:18][S:17][CH:16]=2)[N:3]=1)[CH3:22]

Participants

7

Reactant 3

HCID 7912DiisopropylamineHCID 109974264,4,5,5-Tetramethyl-2-(prop-1-en-2-yl)-1,3,2-dioxaborolaneHCID 66661365Methyl 3-bromo-1-(thiophen-3-yl)-1H-indazole-6-carboxylate

Product 1

HCID 66661623Methyl 3-(prop-1-en-2-yl)-1-(thiophen-3-yl)-1H-indazole-6-carboxylateYield 87%

Reagents, catalysts & solvents 3

HCID 167845palladium(II) acetateCatalystHCID 962WaterSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
100 °C

Procedure

Methyl 3-bromo-1-(thiophen-3-yl)-1H-indazole-6-carboxylate (1.414 g, 4.19 mmol), 2-isopropenyl-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (1.58 ml, 8.41 mmol), diisopropylamine (1.18 ml, 8.40 mmol), triphenylphosphine-3,3′,3″-trisulfonic acid trisodium salt hydrate (275.8 mg, 0.431 mmol), and palladium(II) acetate (48.3 mg, 0.215 mmol) were dissolved in N,N-dimethylformamide (15 ml)/water (5 mL), placed in a sealed tube and heated to 100° C. for 4 h. The reaction was stopped, cooled to room temperature, quenched by addition of saturated aqueous ammonium chloride (20 mL), and the mixture extracted with ethyl acetate (3×20 mL). The combined organic phases were washed with saturated aqueous sodium chloride (1×15 mL), dried (sodium sulfate), filtered, and the solvent evaporated under reduced pressure. The crude product was purified by flash chromatography (RediSep SiO2, 330 g column) on a CombiFlash Rf purification system eluting with ethyl acetate-hexanes (0-15%). The title compound (1.0847 g, 3.64 mmol, 87% yield) was recovered as a white solid. LC-MS: [M+1]=299.2.

Workup

  1. customplaced in a sealed tube
  2. temperaturecooled to room temperature
  3. customquenched by addition of saturated aqueous ammonium chloride (20 mL)
  4. extractionthe mixture extracted with ethyl acetate (3×20 mL)
  5. washThe combined organic phases were washed with saturated aqueous sodium chloride (1×15 mL)
  6. dry with materialdried (sodium sulfate)
  7. filtrationfiltered
  8. customthe solvent evaporated under reduced pressure
  9. customThe crude product was purified by flash chromatography (RediSep SiO2, 330 g column) on a CombiFlash Rf purification system
  10. washeluting with ethyl acetate-hexanes (0-15%)

Sources & evidence

ORD record
ord-0fe27ead2d0445369adbddbf9d939284
Source dataset
uspto-grants-2013_10
Patent number
US08569512B2

Reaction notes

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