Benzophenone imine → HCID 68420558, compound

HRID 1983530Notes

Reaction equation

HRID 1983530 reaction equation
Br[C:2]1[C:3]([O:37][CH3:38])=[C:4]2[C:8](=[CH:9][CH:10]=1)[N:7]([C:11]([C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1)([C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1)[C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1)[N:6]=[C:5]2[C:30]1[CH:35]=[CH:34][CH:33]=[C:32]([F:36])[CH:31]=1.CC(C)([O-])C.[Na+].C(=[NH:58])(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.C(OCC)C>[F:36][C:32]1[CH:31]=[C:30]([C:5]2[C:4]3[C:8](=[CH:9][CH:10]=[C:2]([NH2:58])[C:3]=3[O:37][CH3:38])[N:7]([C:11]([C:12]3[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=3)([C:24]3[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=3)[C:18]3[CH:19]=[CH:20][CH:21]=[CH:22][CH:23]=3)[N:6]=2)[CH:35]=[CH:34][CH:33]=1

Participants

7

Reactant 4

HCID 136809Benzophenone imineHCID 634876Binap, (A+-)-HCID 22260730HCID 22260730, compoundHCID 23676156Sodium t-butoxide

Product 1

HCID 68420558HCID 68420558, compound

Reagents, catalysts & solvents 2

HCID 1140TolueneSolventHCID 3283Diethyl EtherSolvent

Conditions

Temperature
80 °C

Procedure

A total of 810 mg of 5-bromo-3-(3-fluoro-phenyl)-4-methoxy-1-trityl-1H-indazole obtained in Production Example II-18-a was dissolved in 7.2 ml of toluene, 194 mg of sodium t-butoxide, 0.29 ml of benzophenoneimine, 135 mg of 2,2′-bis(diphenylphosphino)-1,1′-binaphthyl and 74.5 mg of tris(dibenzylideneacetone)bispalladium were added, and the mixture was stirred at 80° C. in an atmosphere of nitrogen gas for 8 hours. The reaction mixture was cooled to room temperature, and diethyl ether was added. The mixture was filtrated through Celite, and the filtrate was evaporated. The resulting residue was dissolved in 7.2 ml of tetrahydrofuran and 0.36 ml of 2 N hydrochloric acid was added, followed by stirring at room temperature for 3 hours. Saturated aqueous sodium hydrogencarbonate solution was added to the reaction mixture and the mixture was extracted with diethyl ether. The resulting organic layer was washed with brine, dried over magnesium sulfate and the solvent was evaporated. The residue was purified and separated by silica gel column chromatography (ethyl acetate:hexane=1:3), to give 426 mg of the title compound as reddish brown crystals.

Workup

  1. temperatureThe reaction mixture was cooled to room temperature
  2. filtrationThe mixture was filtrated through Celite
  3. customthe filtrate was evaporated
  4. dissolutionThe resulting residue was dissolved in 7.2 ml of tetrahydrofuran
  5. addition0.36 ml of 2 N hydrochloric acid was added
  6. stirringby stirring at room temperature for 3 hours
  7. additionSaturated aqueous sodium hydrogencarbonate solution was added to the reaction mixture
  8. extractionthe mixture was extracted with diethyl ether
  9. washThe resulting organic layer was washed with brine
  10. dry with materialdried over magnesium sulfate
  11. customthe solvent was evaporated
  12. customThe residue was purified
  13. customseparated by silica gel column chromatography (ethyl acetate:hexane=1:3)

Sources & evidence

ORD record
ord-cf21d382c6574130bf5209d5f417830f
Source dataset
uspto-grants-2009_06
Patent number
US07541376B2

Reaction notes

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