Cesium carbonate → Methyl 3-(2-chlorophenyl)-1-(4-methylphenyl)-1H-indazole-6-carboxylate

HRID 1047624Notes

Reaction equation

HRID 1047624 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:20]=[CH:19][C:18]([CH3:21])=[CH:17][CH:16]=2)[N:3]=1.[Cl:22][C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][C:24]=1B(O)O.C(=O)([O-])[O-].[Cs+].[Cs+]>[Cu]Cl.C1(P(C2C=CC=CC=2)[C-]2C=CC=C2)C=CC=CC=1.[C-]1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=C1.[Fe+2].C([O-])(=O)C.[Pd+2].C([O-])(=O)C.CN(C)C=O>[Cl:22][C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][C:24]=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:15]2[CH:20]=[CH:19][C:18]([CH3:21])=[CH:17][CH:16]=2)[N:3]=1

Participants

8

Reactant 3

HCID 10796Cesium carbonateHCID 27343222-Chlorophenylboronic acidHCID 66661548methyl 3-bromo-1-(4-methylphenyl)-1H-indazole-6-carboxylate

Product 1

HCID 66661211Methyl 3-(2-chlorophenyl)-1-(4-methylphenyl)-1H-indazole-6-carboxylateYield 76.3%

Reagents, catalysts & solvents 4

HCID 62652Cuprous chlorideCatalystHCID 167845palladium(II) acetateCatalystHCID 635956Ferrocene-1,1'-bis-(diphenylphosphine)CatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
90 °C

Procedure

To a mixture of methyl 3-bromo-1-(4-methylphenyl)-1H-indazole-6-carboxylate (0.30 g, 0.87 mmol), 2-chlorophenylboronic acid (0.21 g, 1.34 mmol), cesium carbonate (0.86 g, 2.64 mmol), copper(I) chloride (91.6 mg, 0.93 mmol), 1,1′-bis(diphenylphosphino)ferrocene (51.6 mg, 0.09 mmol) and palladium(II) acetate (9.8 mg, 0.04 mmol) under argon was added N,N-dimethylformamide (4.3 mL). The mixture stirred in a sealed tube at 90° C. for 30 min. The mixture was cooled to ambient temperature and quenched with saturated sodium bicarbonate (15 mL). The mixture was extracted with ethyl acetate (3×15 mL). The combined organic layers were washed with saturated aqueous sodium chloride (1×10 mL), dried over sodium sulfate, filtered and concentrated under reduced pressure. Purification by silica gel chromatography (100% hexanes→95% hexanes/ethyl acetate) gave the title compound (0.25 g): LC-MS [M+1]=377.2.

Workup

  1. temperatureThe mixture was cooled to ambient temperature
  2. customquenched with saturated sodium bicarbonate (15 mL)
  3. extractionThe mixture was extracted with ethyl acetate (3×15 mL)
  4. washThe combined organic layers were washed with saturated aqueous sodium chloride (1×10 mL)
  5. dry with materialdried over sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure
  8. customPurification by silica gel chromatography (100% hexanes→95% hexanes/ethyl acetate)

Sources & evidence

ORD record
ord-e9629636ba6e49c7b9eee96aa8f5d390
Source dataset
uspto-grants-2013_10
Patent number
US08569512B2

Reaction notes

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