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

HRID 1047630Notes

Reaction equation

HRID 1047630 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.[F:22][C:23]1[CH:28]=[CH:27][CH:26]=[C:25]([F:29])[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>[F:22][C:23]1[CH:28]=[CH:27][CH:26]=[C:25]([F:29])[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 27343362,6-Difluorophenylboronic acidHCID 66661548methyl 3-bromo-1-(4-methylphenyl)-1H-indazole-6-carboxylate

Product 1

HCID 66661289Methyl 3-(2,6-difluorophenyl)-1-(4-methylphenyl)-1H-indazole-6-carboxylateYield 53.6%

Reagents, catalysts & solvents 4

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

Conditions

Temperature
90 °C

Procedure

Methyl 3-bromo-1-(4-methylphenyl)-1H-indazole-6-carboxylate 173.7 mg, 0.503 mmol), 2,6-difluorophenylboronic acid, pinacol ester (183.4 mg, 0.764 mmol), Cs2CO3 (505.1 mg, 1.550 mmol), copper(I) chloride (52.7 mg, 0.532 mmol), 1,1′-bisdiphenylphosphino ferrocene (29.3 mg, 0.053 mmol), and palladium(II) acetate (6.5 mg, 0.029 mmol) were placed in a 10-20 mL microwave vial under Ar. N,N-dimethylformamide (2.50 mL) was added and the vessel sealed. The reaction mixture was heated to 90° C. and allowed to stir for 30 min. The reaction was stopped, quenched by addition of saturated aqueous ammonium chloride (15 mL), and extracted with ethyl acetate (3×15 mL). The combined organic phases were washed with saturated aqueous ammonium chloride (1×15 mL), saturated aqueous sodium chloride (1×10 mL), dried (sodium sulfate), and concentrated under reduced pressure. The crude product was purified by flash chromatography (RediSep SiO2, 24 g column) on a CombiFlash purification system eluting with ethyl acetate-hexanes (0-10%). The title compound (102.1 mg, 0.270 mmol, 53.6% yield) was recovered as a white solid. LC-MS: [M+1]=379.2.

Workup

  1. customthe vessel sealed
  2. customquenched by addition of saturated aqueous ammonium chloride (15 mL)
  3. extractionextracted with ethyl acetate (3×15 mL)
  4. washThe combined organic phases were washed with saturated aqueous ammonium chloride (1×15 mL), saturated aqueous sodium chloride (1×10 mL)
  5. dry with materialdried (sodium sulfate)
  6. concentrationconcentrated under reduced pressure
  7. customThe crude product was purified by flash chromatography (RediSep SiO2, 24 g column) on a CombiFlash purification system
  8. washeluting with ethyl acetate-hexanes (0-10%)

Sources & evidence

ORD record
ord-61ed6e377dbd4c33bc9c77c9e53e4f3f
Source dataset
uspto-grants-2013_10
Patent number
US08569512B2

Reaction notes

Loading…