1,1'-Carbonyldiimidazole → N-Methoxy-N-methyl-1H-indazole-3-carboxamide

HRID 218458

Reaction equation

HRID 218458 reaction equation
[C:1]([C:4]1[C:12]2[C:7](=[CH:8][CH:9]=[CH:10][CH:11]=2)[NH:6][N:5]=1)(O)=[O:2].C(N1C=CN=C1)(N1C=CN=C1)=O.Cl.[CH3:26][NH:27][O:28][CH3:29]>CN(C=O)C>[CH3:29][O:28][N:27]([CH3:26])[C:1]([C:4]1[C:12]2[C:7](=[CH:8][CH:9]=[CH:10][CH:11]=2)[NH:6][N:5]=1)=[O:2]

Participants

5

Reactant 3

HCID 682631,1'-CarbonyldiimidazoleHCID 78250Indazole-3-carboxylic acidHCID 81138Methanamine, N-methoxy-, hydrochloride (1:1)

Product 1

HCID 16036867N-Methoxy-N-methyl-1H-indazole-3-carboxamideYield 81.4%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
65 °C

Procedure

3-Carboxyindazole (10 g, 61.7 mmol) in DMF (100 mL) was treated with carbonyldiimidazole (11 g, 67.84 mmol) at rt with gas evolution for 15 min, after which the reaction mixture was heated up to 65° C. for 2 hours. After cooling to rt, N,O-dimethylhydroxyamine-HCl (4.14 g, 67.8 mmol) was added and the mixture was heated to 65° C. overnight. The reaction was cooled, quenched with water, extracted with CH2Cl2 and washed with water. The combined organic phase was dried and concentrated to afford N-methoxy-N-methyl-1H-indazole-3-carboxamide (10.3 g, 81.4%).

Workup

  1. temperatureAfter cooling to rt
  2. temperaturethe mixture was heated to 65° C. overnight
  3. temperatureThe reaction was cooled
  4. customquenched with water
  5. extractionextracted with CH2Cl2
  6. washwashed with water
  7. customThe combined organic phase was dried
  8. concentrationconcentrated

Sources & evidence

ORD record
ord-c678d9ae3a624567bfad52efe9f10168
Source dataset
uspto-grants-2012_06
Patent number
US08198456B2

Linked notes

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