Benzophenone imine → 3-(3-Fluoro-phenyl)-7-methyl-1-trityl-1H-indazol-5-ylamine

HRID 503194Notes

Reaction equation

HRID 503194 reaction equation
Br[C:2]1[CH:3]=[C:4]2[C:8](=[C:9]([CH3:11])[CH:10]=1)[N:7]([C:12]([C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1)([C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1)[C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1)[N:6]=[C:5]2[C:31]1[CH:36]=[CH:35][CH:34]=[C:33]([F:37])[CH:32]=1.C(=[NH:51])(C1C=CC=CC=1)C1C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC3C(=CC=CC=3)C=2C2C3C(=CC=CC=3)C=CC=2P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>C1(C)C=CC=CC=1.O.C(OCC)(=O)C>[F:37][C:33]1[CH:32]=[C:31]([C:5]2[C:4]3[C:8](=[C:9]([CH3:11])[CH:10]=[C:2]([NH2:51])[CH:3]=3)[N:7]([C:12]([C:13]3[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=3)([C:25]3[CH:26]=[CH:27][CH:28]=[CH:29][CH:30]=3)[C:19]3[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=3)[N:6]=2)[CH:36]=[CH:35][CH:34]=1

Participants

7

Reactant 3

HCID 136809Benzophenone imineHCID 634876Binap, (A+-)-HCID 222607405-Bromo-3-(3-fluorophenyl)-7-methyl-1-trityl-1H-indazole

Product 1

HCID 684216763-(3-Fluoro-phenyl)-7-methyl-1-trityl-1H-indazol-5-ylamineYield 48.7%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 1140TolueneSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of 2.0 g of 5-bromo-3-(3-fluorophenyl)-7-methyl-1-trityl-1H-indazole obtained in Production Example II-9-c in 20 ml toluene at room temperature were added 0.73 g of benzophenoneimine, 95 mg of tris(dibenzylideneacetone)(chloroform)dipalladium(0), 0.17 g of 2,2′-bis(diphenylphosphino)-1,1′-binaphthyl and 0.53 g of sodium tert-butyrate, and the mixture was heated under reflux for one day. The mixture was diluted with water and ethyl acetate, and the organic layer was sequentially washed with saturated aqueous ammonium chloride solution and brine, dried over anhydrous magnesium sulfate, and the solvent was evaporated. The residue was dissolved in 30 ml of tetrahydrofuran, 10 ml of 5 N hydrochloric acid was added at room temperature, and the mixture was stirred at the same temperature for 30 minutes. The reaction mixture was neutralized with 5 N aqueous sodium hydroxide solution and was extracted with ethyl acetate. The organic layer was washed with brine, dried over anhydrous magnesium sulfate, and the solvent was evaporated. The crude product was purified and separated by silica gel column chromatography (ethyl acetate:n-hexane=1:10 to 1:3), and the resulting obtained crystals were washed with diethyl ether, to give 0.86 g of the title compound as colorless crystals.

Workup

  1. temperaturethe mixture was heated
  2. temperatureunder reflux for one day
  3. washthe organic layer was sequentially washed with saturated aqueous ammonium chloride solution and brine
  4. dry with materialdried over anhydrous magnesium sulfate
  5. customthe solvent was evaporated
  6. dissolutionThe residue was dissolved in 30 ml of tetrahydrofuran
  7. addition10 ml of 5 N hydrochloric acid was added at room temperature
  8. extractionwas extracted with ethyl acetate
  9. washThe organic layer was washed with brine
  10. dry with materialdried over anhydrous magnesium sulfate
  11. customthe solvent was evaporated
  12. customThe crude product was purified
  13. customseparated by silica gel column chromatography (ethyl acetate:n-hexane=1:10 to 1:3)
  14. customthe resulting obtained crystals
  15. washwere washed with diethyl ether

Sources & evidence

ORD record
ord-cd6f445819ad41d6b6a55c79c5c857a3
Source dataset
uspto-grants-2010_08
Patent number
US07776890B2

Reaction notes

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