Benzophenone imine → 1-Methyl-1H-indazol-3-amine

HRID 2404371Notes

Reaction equation

HRID 2404371 reaction equation
CC1(C)C2C(=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=CC=2)OC2C(P(C3C=CC=CC=3)C3C=CC=CC=3)=CC=CC1=2.Br[C:44]1[CH:52]=[CH:51][CH:50]=[C:49]2[C:45]=1[CH:46]=[N:47][N:48]2[CH3:53].C(=[NH:67])(C1C=CC=CC=1)C1C=CC=CC=1.CC(C)([O-])C.[Na+]>C1(C)C=CC=CC=1.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[CH3:53][N:48]1[C:49]2[C:45](=[CH:44][CH:52]=[CH:51][CH:50]=2)[C:46]([NH2:67])=[N:47]1

Participants

7

Reactant 4

HCID 136809Benzophenone imineHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 225589864-Bromo-1-methyl-1H-indazoleHCID 23676156Sodium t-butoxide

Product 1

HCID 122913171-Methyl-1H-indazol-3-amine

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 1140TolueneSolvent2×

Procedure

A mixture of palladium(II) acetate (82 mg, 2 mol %) and Xantphos (287 mg, 3 mol %) in toluene (10 mL) was stirred for 5 minutes at ambient temperature. To the solution was added a solution of Example 4B (3.68 g, 17.4 mmol) and benzophenone imine (3.00 g, 17.4 mmol) in toluene (30 mL). The mixture was evacuated and purged with nitrogen two times, then stirred at ambient temperature for 15 minutes. Sodium tert-butoxide (1.90 g, 24.4 mmol) was added and the mixture was evacuated and purged with nitrogen. The mixture was heated at between 80 and 85° C. for 2 hours, cooled to ambient temperature, and diluted with water (30 mL). The layers were partitioned and the aqueous layer was extracted with additional toluene (20 mL). The combined organic layers were stirred with 6 N HCl (10 mL) for 1 hour, then 40 mL of water was added to dissolve the solids. The toluene layer was discarded and the aqueous layer filtered to remove insoluble material. The aqueous layer was adjusted to pH 14 with the addition of 50% NaOH and the resulting solid was filtered and dried to provide the title compound. MS (DCI/NH3) m/z 202 (M+H)+.

Workup

  1. customThe mixture was evacuated
  2. custompurged with nitrogen two times
  3. stirringstirred at ambient temperature for 15 minutes
  4. customthe mixture was evacuated
  5. custompurged with nitrogen
  6. temperatureThe mixture was heated at between 80 and 85° C. for 2 hours
  7. temperaturecooled to ambient temperature
  8. additiondiluted with water (30 mL)
  9. customThe layers were partitioned
  10. extractionthe aqueous layer was extracted with additional toluene (20 mL)
  11. stirringThe combined organic layers were stirred with 6 N HCl (10 mL) for 1 hour
  12. addition40 mL of water was added
  13. dissolutionto dissolve the solids
  14. filtrationthe aqueous layer filtered
  15. customto remove insoluble material
  16. additionThe aqueous layer was adjusted to pH 14 with the addition of 50% NaOH
  17. filtrationthe resulting solid was filtered
  18. customdried

Sources & evidence

ORD record
ord-9b46d8f101404c6d80e4f2c6af8c3a71
Source dataset
uspto-grants-2014_08
Patent number
US08802711B2

Reaction notes

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