Pyridine → 1-[3-Chloro-4-(methyloxy)phenyl]-4-[(phenylmethyl)oxy]-1H-indazole

HRID 2423087Notes

Reaction equation

HRID 2423087 reaction equation
[C:1]1([CH2:7][O:8][C:9]2[CH:17]=[CH:16][CH:15]=[C:14]3[C:10]=2[CH:11]=[N:12][NH:13]3)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[Cl:18][C:19]1[CH:20]=[C:21](B(O)O)[CH:22]=[CH:23][C:24]=1[O:25][CH3:26].N1C=CC=CC=1>C(Cl)Cl.C([O-])(=O)C.[Cu+2].C([O-])(=O)C>[Cl:18][C:19]1[CH:20]=[C:21]([N:13]2[C:14]3[C:10](=[C:9]([O:8][CH2:7][C:1]4[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=4)[CH:17]=[CH:16][CH:15]=3)[CH:11]=[N:12]2)[CH:22]=[CH:23][C:24]=1[O:25][CH3:26]

Participants

6

Reactant 3

HCID 1049PyridineHCID 32475223-Chloro-4-methoxybenzeneboronic acidHCID 231344734-(Benzyloxy)-1h-indazole

Product 1

HCID 592729571-[3-Chloro-4-(methyloxy)phenyl]-4-[(phenylmethyl)oxy]-1H-indazoleYield 57.8%

Reagents, catalysts & solvents 2

HCID 8895Cupric acetateCatalystHCID 6344DichloromethaneSolvent

Procedure

The 4-[(phenylmethyl)oxy]-1H-indazole (D1) (500 mg, 2.23 mmol), the [3-chloro-4-(methyloxy)phenyl]boronic acid (831 mg, 4.46 mmol), copper (II) acetate (608 mg, 3.345 mmol), powdered molecular sieves (400 mg) and pyridine (0.36 mL, 4.46 mmol) in DCM (75 mL) were stirred at room temperature in the presence of air. After 5 days the mixture was filtered through a pad of celite and washed with water. The aqueous was re-extracted with DCM and the combined organics were washed with brine and dried over MgSO4. The crude (1.06 g) was purified by flash chromatography (Biotage SP4, 40+M silica column) with a gradient of EtOAc (0 to 20%) in hexane to afford 470 mg of title compound (D33) containing an impurity.

Workup

  1. filtrationAfter 5 days the mixture was filtered through a pad of celite
  2. washwashed with water
  3. extractionThe aqueous was re-extracted with DCM
  4. washthe combined organics were washed with brine
  5. dry with materialdried over MgSO4
  6. customThe crude (1.06 g) was purified by flash chromatography (Biotage SP4, 40+M silica column) with a gradient of EtOAc (0 to 20%) in hexane

Sources & evidence

ORD record
ord-2b418707aeb44056974d462e5bf00e6d
Source dataset
uspto-grants-2011_06
Patent number
US07960563B2

Reaction notes

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