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

HRID 2410074Notes

Reaction equation

HRID 2410074 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 2C (3.68 g, 17.4 mmol) and benzophenone imine (3.0 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 (1.9 g, 1.4 eq) was added and the mixture was evacuated and purged with nitrogen. The mixture was heated to between 80-85° C. for 2 hours, cooled to ambient temperature and diluted with water (30 mL). The aqueous layer was separated and extracted with additional toluene (20 mL). The combined organic layers were stirred with 6 N HCl (10 mL) for 1 hour and 40 mL of water added to dissolve the solids. The toluene layer was discarded and aqueous layer filtered to remove insoluble material. The aqueous layer was adjusted to the pH of 14 with 50% NaOH and filtered to provide the title compound. The solid was dissolved in acetonitrile (25 mL) followed by the slow addition of 12 M HCl to adjust the pH to 1. The precipitate was filtered off, washed with water and dried to provide the hydrochloride salt of the title compound. 1H NMR (DMSO) δ 8.03 (d, 1H), 7.02 (dd, 1H), 6.64 (dt, 1H), 6.14 (dd, 1H), 5.73 (brs, 2H), 3.90 (s, 3H).

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 to between 80-85° C. for 2 hours
  7. temperaturecooled to ambient temperature
  8. additiondiluted with water (30 mL)
  9. customThe aqueous layer was separated
  10. extractionextracted 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 added
  13. dissolutionto dissolve the solids
  14. filtrationaqueous layer filtered
  15. customto remove insoluble material
  16. filtrationfiltered

Sources & evidence

ORD record
ord-6c758d1d691d4caa97d1736d5d70539d
Source dataset
uspto-grants-2014_08
Patent number
US08815930B2

Reaction notes

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