Sulfuric Acid → HCID 67975956, compound

HRID 706688Notes

Reaction equation

HRID 706688 reaction equation
[CH3:1][C:2]1[N:7]=[C:6]([CH2:8][N:9]2[C:17]3[CH:16]=[CH:15][CH:14]=[C:13]([NH2:18])[C:12]=3[CH:11]=[N:10]2)[CH:5]=[CH:4][CH:3]=1.OS(O)(=O)=O.[Cl:24]N1C(=O)CCC1=O.C(=O)([O-])[O-].[Na+].[Na+]>O.C1COCC1>[Cl:24][C:16]1[C:17]2[N:9]([CH2:8][C:6]3[CH:5]=[CH:4][CH:3]=[C:2]([CH3:1])[N:7]=3)[N:10]=[CH:11][C:12]=2[C:13]([NH2:18])=[CH:14][CH:15]=1

Participants

7

Reactant 4

HCID 1118Sulfuric AcidHCID 10340Sodium CarbonateHCID 31398ChlorosuccinimideHCID 67976246HCID 67976246, compound

Product 1

HCID 67975956HCID 67975956, compoundYield 33.5%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

A solution of 1-((6-methylpyridin-2-yl)methyl)-1H-indazol-4-amine (0.390 g, 1.64 mmol) and THF (8.0 mL) was cooled to −78° C. under N2. H2SO4 (0.0436 mL, 0.818 mmol) was added and the resulting brown suspension was stirred for 5 minutes. N-chlorosuccinimide (0.219 g, 1.64 mmol) was added in one portion and the reaction was stirred at −78° C. for 1 hour. Sodium carbonate (0.173 g, 1.64 mmol) was added and the mixture was warmed to ambient temperature. The mixture was diluted with water (20 mL) and extracted with EtOAc. The combined organic layers were washed with brine and dried over Na2SO4, filtered and concentrated. The crude product was purified by column chromatography (5 to 30% EtOH/hexanes). The desired product was found in the lower band from the column but it was contaminated with succinimide, so the product was dissolved in 0.5N HCl and extracted with CHCl3. The aqueous phase was basified with NaHCO3 and extracted with EtOAc. The EtOAc was washed with brine, dried over Na2SO4, filtered and concentrated providing the title compound as a pale orange solid (0.150 g, 33%).

Workup

  1. stirringthe reaction was stirred at −78° C. for 1 hour
  2. extractionextracted with EtOAc
  3. washThe combined organic layers were washed with brine
  4. dry with materialdried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe crude product was purified by column chromatography (5 to 30% EtOH/hexanes)
  8. dissolutionso the product was dissolved in 0.5N HCl
  9. extractionextracted with CHCl3
  10. extractionextracted with EtOAc
  11. washThe EtOAc was washed with brine
  12. dry with materialdried over Na2SO4
  13. filtrationfiltered
  14. concentrationconcentrated

Sources & evidence

ORD record
ord-ea07a88fa3bd495c8741104de3471c7f
Source dataset
uspto-grants-2015_11
Patent number
US09174981B2

Reaction notes

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