Pyridine → 4-Bromo-5-fluoro-1-{3-fluoro-4-[(phenylmethyl)oxy]phenyl}-1H-indazole

HRID 2423075Notes

Reaction equation

HRID 2423075 reaction equation
[Br:1][C:2]1[C:10]([F:11])=[CH:9][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.B(O)O>C([O-])(=O)C.[Cu+2].C([O-])(=O)C>[Br:1][C:2]1[C:10]([F:11])=[CH:9][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 4

HCID 1049PyridineHCID 61668Boronic AcidHCID 27377884-Benzyloxy-3-fluorophenylboronic AcidHCID 592729794-Bromo-5-fluoro-1H-indazole

Product 1

HCID 592729594-Bromo-5-fluoro-1-{3-fluoro-4-[(phenylmethyl)oxy]phenyl}-1H-indazoleYield 49.7%

Reagents, catalysts & solvents 1

HCID 8895Cupric acetateCatalyst

Procedure

A mixture of 4-bromo-5-fluoro-1H-indazole (D15) (1.008 g, 4.69 mmol), {3-fluoro-4-[(phenylmethyl)oxy]phenyl}boronic acid 1.730 g, 7.03 mmol), copper(II) acetate (1.277 g, 7.03 mmol) and pyridine (0.758 mL, 0.742 g, 9.38 mmol) were stirred together vigorously under an air atmosphere with powdered 4A molecular sieves (5 g) at room temperature. After 6 days another 580 mg of boronic acid were added and stirring continued for a further 24 hrs. The mixture was filtered through celite, the celite was washed with dichloromethane and the combined filtrate was washed with water, dried over Na2SO4 and evaporated. Chromatography (silica gel, 0-100% dichloromethane in isohexane), followed by trituration of the product with diethyl ether gave the title compound (D16) (0.968 g) as a white solid.

Workup

  1. filtrationThe mixture was filtered through celite
  2. washthe celite was washed with dichloromethane
  3. washthe combined filtrate was washed with water
  4. dry with materialdried over Na2SO4
  5. customevaporated

Sources & evidence

ORD record
ord-5178476d3d7c460bb5fc025e7ee1b0d6
Source dataset
uspto-grants-2011_06
Patent number
US07960563B2

Reaction notes

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