Pyridine → 1-{3,5-Difluoro-4-[(phenyl methyl)oxy]phenyl}-4-[(phenylmethyl)oxy]-1H-indazole

HRID 2423089Notes

Reaction equation

HRID 2423089 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.[F:18][C:19]1[CH:20]=[C:21](B(O)O)[CH:22]=[C:23]([F:33])[C:24]=1[O:25][CH2:26][C:27]1[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=1.N1C=CC=CC=1>ClCCl.C([O-])(=O)C.[Cu+2].C([O-])(=O)C>[F: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]=[C:23]([F:33])[C:24]=1[O:25][CH2:26][C:27]1[CH:28]=[CH:29][CH:30]=[CH:31][CH:32]=1

Participants

6

Reactant 3

HCID 1049PyridineHCID 231344734-(Benzyloxy)-1h-indazoleHCID 54758874(4-(Benzyloxy)-3,5-difluorophenyl)boronic acid

Product 1

HCID 592729551-{3,5-Difluoro-4-[(phenyl methyl)oxy]phenyl}-4-[(phenylmethyl)oxy]-1H-indazole

Reagents, catalysts & solvents 2

HCID 8895Cupric acetateCatalystHCID 6344DichloromethaneSolvent

Procedure

To a solution of 4-[(phenylmethyl)oxy]-1H-indazole (D1) (280 mg, 1.25 mmol) in dichloromethane (20 mL) was added {3,5-difluoro-4-[(phenylmethyl)oxy]phenyl}boronic acid {DE patent application 4236105} (660 mg, 2.50 mmol), pyridine (0.202 mL, 2.50 mmol), copper acetate (340 mg, 1.88 mmol) and powdered 4A molecular sieves (500 mg). The reaction mixture was stirred at room temperature in the presence of air for 6 days. Celite was added to the mixture then the mixture was filtered through a pad of celite and then the filtrate was washed with water. After separation of the layers, the aqueous phase was re-extracted with dichloromethane. The combined organic layers were dried over magnesium sulphate, filtered and concentrated. The product was purified by silica gel chromatography eluting with 5-100% ethyl acetate in hexane to yield the title compound (D35 (257 mg).

Workup

  1. additionCelite was added to the mixture
  2. filtrationthe mixture was filtered through a pad of celite
  3. washthe filtrate was washed with water
  4. customAfter separation of the layers
  5. extractionthe aqueous phase was re-extracted with dichloromethane
  6. dry with materialThe combined organic layers were dried over magnesium sulphate
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customThe product was purified by silica gel chromatography
  10. washeluting with 5-100% ethyl acetate in hexane

Sources & evidence

ORD record
ord-f63ead05786c4eb89b6ac17b49fe0f2f
Source dataset
uspto-grants-2011_06
Patent number
US07960563B2

Reaction notes

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