Chloroacetyl chloride → 2-chloro-N-(1H-indazol-5-yl)acetamide

HRID 1269725Notes

Reaction equation

HRID 1269725 reaction equation
[Cl:1][CH2:2][C:3](Cl)=[O:4].[NH2:6][C:7]1[CH:8]=[C:9]2[C:13](=[CH:14][CH:15]=1)[NH:12][N:11]=[CH:10]2.C(N(CC)CC)C.C(=O)([O-])[O-].[Na+].[Na+]>O1CCCC1.O>[Cl:1][CH2:2][C:3]([NH:6][C:7]1[CH:8]=[C:9]2[C:13](=[CH:14][CH:15]=1)[NH:12][N:11]=[CH:10]2)=[O:4]

Participants

7

Reactant 4

HCID 6577Chloroacetyl chlorideHCID 8471TriethylamineHCID 10340Sodium CarbonateHCID 880121H-Indazol-5-amine

Product 1

HCID 171644632-chloro-N-(1H-indazol-5-yl)acetamideYield 46%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent2×

Procedure

Chloroacetyl chloride (3.14 ml, 39.4 mmol) was added to a solution of 5-aminoindazole (5.0 g, 37.5 mmol) in tetrahydrofuran (100 ml) at room temperature, followed by adding thereto a solution of triethylamine (5.76 ml, 41.3 mmol) in tetrahydrofuran (30 ml) at 0° C., and the resulting mixture was stirred at 0° C. for 30 minutes. Subsequently, a saturated aqueous sodium carbonate solution and then water were added to the reaction solution, followed by extraction with ethyl acetate. The organic layer was dried over anhydrous magnesium sulfate and distilled under reduced pressure to remove the solvent, and the resulting residue was suspended in ethanol and stirred, followed by filtration. To a solution of the solid collected by the filtration and dissolved in a mixture of tetrahydrofuran (25 ml) and methanol (25 ml) was added a 2N-aqueous lithium hydroxide solution (9.3 ml) at 0° C., and stirred at room temperature for 30 minutes. Then, the reaction solution was poured into water and extracted with ethyl acetate. The organic layer was washed with a saturated aqueous sodium chloride solution and then dried over anhydrous magnesium sulfate. The solvent was distilled off under reduced pressure to obtain 2-chloro-N-(1H-indazol-5-yl)acetamide (1.90 g, 46%).

Workup

  1. additionby adding
  2. extractionfollowed by extraction with ethyl acetate
  3. dry with materialThe organic layer was dried over anhydrous magnesium sulfate
  4. distillationdistilled under reduced pressure
  5. customto remove the solvent
  6. filtrationfollowed by filtration
  7. filtrationTo a solution of the solid collected by the filtration
  8. dissolutiondissolved in a mixture of tetrahydrofuran (25 ml) and methanol (25 ml)
  9. additionwas added a 2N-aqueous lithium hydroxide solution (9.3 ml) at 0° C.
  10. stirringstirred at room temperature for 30 minutes
  11. additionThen, the reaction solution was poured into water
  12. extractionextracted with ethyl acetate
  13. washThe organic layer was washed with a saturated aqueous sodium chloride solution
  14. dry with materialdried over anhydrous magnesium sulfate
  15. distillationThe solvent was distilled off under reduced pressure

Sources & evidence

ORD record
ord-2337541c6bd146d09fdd8ac63c7a6f03
Source dataset
uspto-grants-2007_04
Patent number
US07199147B2

Reaction notes

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