Pyridine → 4-Bromo-1-{3-fluoro-4-[(phenylmethyl)oxy]phenyl}-1H-indazole

HRID 2423092Notes

Reaction equation

HRID 2423092 reaction equation
[Br:1][C:2]1[CH:10]=[CH:9][CH:8]=[C:7]2[C:3]=1[CH:4]=[N:5][NH:6]2.[CH2:11]([O:18][C:19]1[CH:24]=[CH:23][C:22](B(O)O)=[CH:21][C:20]=1[F:28])[C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1.N1C=CC=CC=1>ClCCl.C([O-])(=O)C.[Cu+2].C([O-])(=O)C>[Br:1][C:2]1[CH:10]=[CH:9][CH:8]=[C:7]2[C:3]=1[CH:4]=[N:5][N:6]2[C:22]1[CH:23]=[CH:24][C:19]([O:18][CH2:11][C:12]2[CH:13]=[CH:14][CH:15]=[CH:16][CH:17]=2)=[C:20]([F:28])[CH:21]=1

Participants

6

Reactant 3

HCID 1049PyridineHCID 27377884-Benzyloxy-3-fluorophenylboronic AcidHCID 223525484-bromo-1H-indazole

Product 1

HCID 592729654-Bromo-1-{3-fluoro-4-[(phenylmethyl)oxy]phenyl}-1H-indazoleYield 60.3%

Reagents, catalysts & solvents 2

HCID 8895Cupric acetateCatalystHCID 6344DichloromethaneSolvent

Procedure

To a solution of 4-bromo-1H-indazole (4.32 g, 21.9 mmol) in dichloromethane (100 mL) was added 4-benzyloxy-3-fluorobenzeneboronic acid (10.8 g, 43.9 mmol), pyridine (3.5 mL, 43.3 mmol), copper acetate (5.9 g, 32.6 mmol) and powdered 4A molecular sieves (5 g). The reaction mixture was stirred at room temperature in the presence of air for 5 days. Celite was added to the reaction mixture and the mixture stirred for 5 minutes. The mixture was then filtered through a pad of celite and washed with dichloromethane and then the filtrate concentrated in vacuo. The residue was diluted in dichloromethane and water. After separation of the layers, the aqueous phase was extracted with dichloromethane (×4). The combined organic layers were dried over magnesium sulphate, filtered and concentrated in vacuo. The product was purified by silica gel chromatography eluting with 10-80% dichloromethane in hexane to yield the title compound (D38) (5.25 g).

Workup

  1. additionCelite was added to the reaction mixture
  2. stirringthe mixture stirred for 5 minutes
  3. filtrationThe mixture was then filtered through a pad of celite
  4. washwashed with dichloromethane
  5. concentrationthe filtrate concentrated in vacuo
  6. additionThe residue was diluted in dichloromethane
  7. customAfter separation of the layers
  8. extractionthe aqueous phase was extracted with dichloromethane (×4)
  9. dry with materialThe combined organic layers were dried over magnesium sulphate
  10. filtrationfiltered
  11. concentrationconcentrated in vacuo
  12. customThe product was purified by silica gel chromatography
  13. washeluting with 10-80% dichloromethane in hexane

Sources & evidence

ORD record
ord-db61be125077400f86793ce70cef133e
Source dataset
uspto-grants-2011_06
Patent number
US07960563B2

Reaction notes

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