Methyl iodide → Methyl 3-iodo-1-methyl-1H-indazole-5-carboxylate

HRID 246337Notes

Reaction equation

HRID 246337 reaction equation
[CH3:1][O:2][C:3]([C:5]1[CH:6]=[C:7]2[C:11](=[CH:12][CH:13]=1)[NH:10][N:9]=[C:8]2[I:14])=[O:4].[CH3:15]C([O-])(C)C.[K+].IC>C1COCC1>[CH3:1][O:2][C:3]([C:5]1[CH:6]=[C:7]2[C:11](=[CH:12][CH:13]=1)[N:10]([CH3:15])[N:9]=[C:8]2[I:14])=[O:4]

Participants

5

Reactant 3

HCID 6328Methyl iodideHCID 23665647Potassium tert-butoxideHCID 178497396HCID 178497396, compound

Product 1

HCID 71279594Methyl 3-iodo-1-methyl-1H-indazole-5-carboxylateYield 90.8%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of 3-iodo-1H-indazole-5-carboxylic acid methyl ester (1.0 g, 3.31 mmol) in THF (12 mL) at 0° C. was added KOt-Bu (520 mg, 4.63 mmol). The reaction mixture was stirred at 0° C. for 30 min then added iodomethane (0.29 mL, 4.63 mmol). Stirred at 0° C. for 30 min then warmed to room temperature and stirred for 2 h. The reaction was quenched with water and extracted with EtOAc (2×) then with CH2Cl2 (2×). The combined organics were dried over MgSO4 and concentrated to afford 950 mg of 3-iodo-1-methyl-1H-indazole-5-carboxylic acid methyl ester a pale yellow solid. NMR analysis revealed an 8:1 mixture of N1:N2 alkylated regioisomers. Major: 1H NMR (CDCl3, 300 MHz): δ (ppm) 8.25 (s, 1H), 8.13 (dd, J=8.7, 1.5 Hz, 1H), 7.39 (d, J=8.7 Hz, 1H), 4.13 (s, 3H), 3.98 (s, 3H).

Workup

  1. stirringStirred at 0° C. for 30 min
  2. temperaturethen warmed to room temperature
  3. stirringstirred for 2 h
  4. customThe reaction was quenched with water
  5. extractionextracted with EtOAc (2×)
  6. dry with materialThe combined organics were dried over MgSO4
  7. concentrationconcentrated

Sources & evidence

ORD record
ord-555ef4628f1343aeafa24fb8f3a551aa
Source dataset
uspto-grants-2014_02
Patent number
US08658646B2

Reaction notes

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