Pyridine → 5-bromo-1-(4-fluorophenyl)-6-methyl-1H-indazole

HRID 1748816Notes

Reaction equation

HRID 1748816 reaction equation
[Br:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][C:10]=1[CH3:11])[NH:7][N:6]=[CH:5]2.[F:12][C:13]1[CH:18]=[CH:17][C:16](B(O)O)=[CH:15][CH:14]=1.N1C=CC=CC=1>C(Cl)Cl.C(O[Cu]OC(=O)C)(=O)C>[Br:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][C:10]=1[CH3:11])[N:7]([C:16]1[CH:17]=[CH:18][C:13]([F:12])=[CH:14][CH:15]=1)[N:6]=[CH:5]2

Participants

6

Reactant 3

HCID 1049PyridineHCID 2856454-Fluorophenylboronic acidHCID 247292595-Bromo-6-methyl-1H-indazole

Product 1

HCID 670697705-bromo-1-(4-fluorophenyl)-6-methyl-1H-indazoleYield 64.1%

Reagents, catalysts & solvents 2

HCID 178476681HCID 178476681, compoundCatalystHCID 6344DichloromethaneSolvent

Procedure

To a solution of 5-bromo-6-methyl-1H-indazole (2.89 g, 13.69 mmol,) in DCM (137 mL) was added 4-fluorophenylboronic acid (3.83 g, 27.4 mmol), diacetoxycopper (2.48 g, 13.7 mmol), pyridine (2.2 mL, 27.4 mmol) and 4 Å molecular sieves. The reaction was stirred open to air for about 4 h. The reaction mixture was filtered through a pad of Celite® rinsing with EtOAc (80 mL) and then concentrated to about (60 mL) under reduced pressure. Water was added (40 mL) and the layers were separated. The aqueous layer was back extracted with EtOAc (20 mL). The combined organic layers were dried over MgSO4, filtered and concentrated under reduced pressure. The resulting residue was purified by column chromatography (SiO2, EtOAc/heptane 100:0 to 0:20) to afford 5-bromo-1-(4-fluorophenyl)-6-methyl-1H-indazole (2.68 g, 8.78 mmol, 64%). LC-MS (Table 1, Method g) Rt=2.75 min, m/z 305, 307 (M+H)+. 1H NMR (CDCl3) δ 8.07 (s, 1H), 7.98 (s, 1H), 7.69-7.59 (m, 2H), 7.52 (s, 1H), 7.28-7.18 (m, 2H), 2.53 (s, 3H).

Workup

  1. filtrationThe reaction mixture was filtered through a pad of Celite®
  2. washrinsing with EtOAc (80 mL)
  3. concentrationconcentrated to about (60 mL) under reduced pressure
  4. additionWater was added (40 mL)
  5. customthe layers were separated
  6. extractionThe aqueous layer was back extracted with EtOAc (20 mL)
  7. dry with materialThe combined organic layers were dried over MgSO4
  8. filtrationfiltered
  9. concentrationconcentrated under reduced pressure
  10. customThe resulting residue was purified by column chromatography (SiO2, EtOAc/heptane 100:0 to 0:20)

Sources & evidence

ORD record
ord-aa9e2a5ac7644cff9494f05d9249d7a2
Source dataset
uspto-grants-2015_10
Patent number
US09150592B2

Reaction notes

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