Acetic Anhydride → Methyl 5-bromo-1H-indazole-7-carboxylate

HRID 2284585Notes

Reaction equation

HRID 2284585 reaction equation
C(OC(=O)C)(=O)C.[NH2:8][C:9]1[C:18]([CH3:19])=[CH:17][C:16]([Br:20])=[CH:15][C:10]=1[C:11]([O:13][CH3:14])=[O:12].C([O-])(=O)C.[K+].[N+:26]([O-])(OCCC(C)C)=O>C(Cl)(Cl)Cl>[Br:20][C:16]1[CH:17]=[C:18]2[C:9](=[C:10]([C:11]([O:13][CH3:14])=[O:12])[CH:15]=1)[NH:8][N:26]=[CH:19]2

Participants

6

Reactant 4

HCID 7918Acetic AnhydrideHCID 10985Isoamyl nitrateHCID 517044Potassium AcetateHCID 2763413Methyl 2-amino-5-bromo-3-methylbenzoate

Product 1

HCID 24728927Methyl 5-bromo-1H-indazole-7-carboxylateYield 43.3%

Reagents, catalysts & solvents 1

HCID 6212ChloroformSolvent

Conditions

Temperature
90 °C

Procedure

Acetic anhydride (4.5 g, 4.1 mL, 44 mmol) was added dropwise to the homogenous solution of methyl 2-amino-5-bromo-3-methylbenzoate (4.72 g, 19 mmol) in chloroform (55 mL) over a period of 20 min at room temperature and allowed to stir for 1 h. Potassium acetate (5.7 g, 58 mmol) and isoamyl nitrate (6.6 g, 7.6 mL, 57 mmol) were added at once to the reaction mixture under nitrogen. The clear reaction mixture turned to dark upon heating at 90° C. The reaction mixture was cooled to room temperature after overnight reflux, concentrated, diluted with water and stirred. The beige solid formed was collected by filtration and dried to obtain methyl 5-bromo-1H-indazole-7-carboxylate (2.1 g, 42%). 1H NMR (DMSO-d6): δ 13.44 (s, 1H), 8.33 (s, 1H), 8.21 (s, 1H), 7.99 (s, 1H), 3.95 (s, 3H).LCMS: rt 6.86 min (A), purity 99%, MS (m/e) 255 (MH+).

Workup

  1. temperatureThe reaction mixture was cooled to room temperature after overnight
  2. temperaturereflux
  3. concentrationconcentrated
  4. additiondiluted with water
  5. stirringstirred
  6. customThe beige solid formed
  7. filtrationwas collected by filtration
  8. customdried

Sources & evidence

ORD record
ord-f53fed7a97ac44a2811cd9b39c4789d7
Source dataset
uspto-grants-2015_09
Patent number
US09145433B2

Reaction notes

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