Dimethylformamide → Methyl 1-methyl-1H-indazole-3-carboxylate

HRID 1581677Notes

Reaction equation

HRID 1581677 reaction equation
N1C2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[C:3]([C:10]([OH:12])=[O:11])=[N:2]1.[C:13]([O-])([O-])=O.[K+].[K+].CI.C[N:22]([CH:24]=O)[CH3:23]>>[CH3:23][N:22]1[C:24]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[C:3]([C:10]([O:12][CH3:13])=[O:11])=[N:2]1

Participants

5

Reactant 4

HCID 6228DimethylformamideHCID 6328Methyl iodideHCID 11430Potassium CarbonateHCID 78250Indazole-3-carboxylic acid

Product 1

HCID 13900574Methyl 1-methyl-1H-indazole-3-carboxylateYield 68%

Conditions

Temperature
50 °C

Procedure

Indazole-3-carboxylic acid (5.0 g, 30 mmole), K2CO3 (12.4 g, 90 mmole), and MeI (9.3 mL, 150 mmole) were combined in dry DMF (100 mL) and heated to 50° C. After 18 hr the mixture was cooled to RT and concentrated in vacuo. The residue was taken up in EtOAc and filtered, and the filtrate was concentrated under reduced pressure. The residue was flash chromatographed on silica gel (25% EtOAc/hexanes) to give the title compound (3.88 g, 68%) as a yellow solid: 1H NMR (300 MHz, CDCl3) δ 8.24 (m, 1H), 7.47 (m, 2H), 7.34 (m, 1H), 4.19 (s, 3H), 4.05 (s, 3H).

Workup

  1. temperatureAfter 18 hr the mixture was cooled to RT
  2. concentrationconcentrated in vacuo
  3. filtrationfiltered
  4. concentrationthe filtrate was concentrated under reduced pressure
  5. customchromatographed on silica gel (25% EtOAc/hexanes)

Sources & evidence

ORD record
ord-73aad798ac9b44ceba078d8beb14501c
Source dataset
uspto-grants-2004_05
Patent number
US06730684B1

Reaction notes

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