Pyridine → 4-Bromo-1-{3-fluoro-4-[(phenylmethyl)oxy]phenyl}-6-methyl-1h-indazole

HRID 2423072Notes

Reaction equation

HRID 2423072 reaction equation
[Br:1][C:2]1[CH:10]=[C:9]([CH3:11])[CH:8]=[C:7]2[C:3]=1[CH:4]=[N:5][NH:6]2.[F:12][C:13]1[CH:14]=[C:15](B(O)O)[CH:16]=[CH:17][C:18]=1[O:19][CH2:20][C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1.N1C=CC=CC=1>C(Cl)Cl.C([O-])(=O)C.[Cu+2].C([O-])(=O)C>[Br:1][C:2]1[CH:10]=[C:9]([CH3:11])[CH:8]=[C:7]2[C:3]=1[CH:4]=[N:5][N:6]2[C:15]1[CH:16]=[CH:17][C:18]([O:19][CH2:20][C:21]2[CH:22]=[CH:23][CH:24]=[CH:25][CH:26]=2)=[C:13]([F:12])[CH:14]=1

Participants

6

Reactant 3

HCID 1049PyridineHCID 27377884-Benzyloxy-3-fluorophenylboronic AcidHCID 247288014-Bromo-6-methyl-1H-indazole

Product 1

HCID 592729664-Bromo-1-{3-fluoro-4-[(phenylmethyl)oxy]phenyl}-6-methyl-1h-indazoleYield 107%

Reagents, catalysts & solvents 2

HCID 8895Cupric acetateCatalystHCID 6344DichloromethaneSolvent

Procedure

The 4-bromo-6-methyl-1H-indazole (950 mg, 4.5 mmol), the {3-fluoro-4-[(phenylmethyl)oxy]phenyl}boronic acid (2.2 g, 9 mmol), copper (II) acetate (1.22 g, 6.75 mmol) and pyridine (0.73 mL, 9 mmol) in DCM (80 mL) were stirred in the presence of molecular sieves (4 A, 2 g) in air. After 40 hours the mixture was filtered through a pad of celite and concentrated to afford 3.3 g of crude material. This was purified by flash chromatography (Biotage SP4, 40+M silica column) with a gradient of EtOAc 0 to 30% in hexane to afford 1.98 g of desired compound (D12) slightly impure but carried forward.

Workup

  1. filtrationAfter 40 hours the mixture was filtered through a pad of celite
  2. concentrationconcentrated
  3. customto afford 3.3 g of crude material
  4. customThis was purified by flash chromatography (Biotage SP4, 40+M silica column) with a gradient of EtOAc 0 to 30% in hexane

Sources & evidence

ORD record
ord-29910b39b6f74713843098eeb127efd8
Source dataset
uspto-grants-2011_06
Patent number
US07960563B2

Reaction notes

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