Potassium Carbonate → 5-(4-Acetylphenyl)-6-chloro-1H-indazole-3-carboxylic acid

HRID 1054811Notes

Reaction equation

HRID 1054811 reaction equation
Br[C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][C:10]=1[Cl:11])[NH:7][N:6]=[C:5]2[C:12]([OH:14])=[O:13].[C:15]([C:18]1[CH:23]=[CH:22][C:21](B(O)O)=[CH:20][CH:19]=1)(=[O:17])[CH3:16].C(=O)([O-])[O-].[K+].[K+]>C1(C)C=CC=CC=1.CCO.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[C:15]([C:18]1[CH:23]=[CH:22][C:21]([C:2]2[CH:3]=[C:4]3[C:8](=[CH:9][C:10]=2[Cl:11])[NH:7][N:6]=[C:5]3[C:12]([OH:14])=[O:13])=[CH:20][CH:19]=1)(=[O:17])[CH3:16]

Participants

7

Reactant 3

HCID 11430Potassium CarbonateHCID 37021224-Acetylphenylboronic acidHCID 866987915-bromo-6-chloro-1H-indazole-3-carboxylic acid

Product 1

HCID 866988035-(4-Acetylphenyl)-6-chloro-1H-indazole-3-carboxylic acidYield 40%

Reagents, catalysts & solvents 3

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 702EthanolSolventHCID 1140TolueneSolvent

Procedure

To a mixture of 5-bromo-6-chloro-1H-indazole-3-carboxylic acid (200 mg, 0.73 mmol) and 4-acetylphenylboronic acid (131 mg, 0.80 mmol) in toluene (2 mL) and EtOH (1 mL) was added 2 N aqueous potassium carbonate solution (1.45 mL, 2.90 mmol). The resulting mixture was degassed with N2 for 10 minutes, treated with [1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium(II) (29 mg, 0.036 mmol), and heated to reflux for 16 hours. The cooled reaction was quenched with saturated NH4Cl and the mixture was filtered. The filtrate was acidified with 1 N HCl to pH 5 and extracted with EtOAc. The organic layer was dried over Na2SO4 and concentrated in vacuo. The resulting crude material was purified by reverse phase chromatography (Biotage C18 column, 0-40% MeCN/water) to give the title compound (82 mg, 40% yield) as a solid. MS (ES+) 315.0 (M+H)+. 1H NMR (400 MHz, DMSO-d6) δ 8.14 (s, 1H), 8.01 (d, J=8.39 Hz, 2H), 7.82 (s, 1H), 7.57 (d, J=8.20 Hz, 2H), 2.60 (s, 3H).

Workup

  1. customThe resulting mixture was degassed with N2 for 10 minutes
  2. temperatureheated
  3. temperatureto reflux for 16 hours
  4. customThe cooled reaction
  5. customwas quenched with saturated NH4Cl
  6. filtrationthe mixture was filtered
  7. extractionextracted with EtOAc
  8. dry with materialThe organic layer was dried over Na2SO4
  9. concentrationconcentrated in vacuo
  10. customThe resulting crude material was purified by reverse phase chromatography (Biotage C18 column, 0-40% MeCN/water)

Sources & evidence

ORD record
ord-c6893c9677404ff696f2a211b5d88a24
Source dataset
uspto-grants-2016_07
Patent number
US09394285B2

Reaction notes

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