Cesium carbonate → HCID 66661228, compound

HRID 1047644Notes

Reaction equation

HRID 1047644 reaction equation
Br[C:2]1[C:10]2[C:5](=[CH:6][CH:7]=[C:8]([C:11]([O:13][CH3:14])=[O:12])[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+]>CN(C)C=O.C([O-])(=O)C.[Pd+2].C([O-])(=O)C.[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]>[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][CH:7]=[C:8]([C:11]([O:13][CH3:14])=[O:12])[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 66661444HCID 66661444, compound

Product 1

HCID 66661228HCID 66661228, compoundYield 71.6%

Reagents, catalysts & solvents 4

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

Conditions

Temperature
100 °C

Procedure

Methyl 3-bromo-1-(4-methylphenyl)-1H-indazole-5-carboxylate (150.3 mg, 0.435 mmol), 2-chlorophenylboronic acid, pinacol ester (210.4 mg, 0.882 mmol), palladium(II) acetate (5.2 mg, 0.023 mmol), copper(I) chloride (88.5 mg, 0.894 mmol), cesium carbonate (431.8 mg, 1.325 mmol), and 1,1′-bisdiphenylphosphino ferrocene (26.4 mg, 0.048 mmol) were dissolved in N,N-dimethylformamide (2200 μl) at 25° C. under Ar. The reaction mixture was warmed to 100° C. and allowed to stir for 3 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 washed with saturated aqueous ammonium chloride (2×10 mL) and saturated aqueous sodium chloride (1×10 mL), dried (sodium sulfate), filtered, and the solvent evaporated under reduced pressure. Crude product purified by flash chromatography (RediSep SiO2, 24 g column) on a CombiFlash Rf purification system eluting with ethyl acetate-hexanes (0-30%). The title compound (117.4 mg, 0.312 mmol, 71.6% yield) was recovered as a light yellow/white solid. LC-MS: [M+1]=377.1.

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 washed with saturated aqueous ammonium chloride (2×10 mL) and saturated aqueous sodium chloride (1×10 mL)
  5. dry with materialdried (sodium sulfate)
  6. filtrationfiltered
  7. customthe solvent evaporated under reduced pressure
  8. customCrude product purified by flash chromatography (RediSep SiO2, 24 g column) on a CombiFlash Rf purification system
  9. washeluting with ethyl acetate-hexanes (0-30%)

Sources & evidence

ORD record
ord-d786f7e2941b499b9685d1624d802516
Source dataset
uspto-grants-2013_10
Patent number
US08569512B2

Reaction notes

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