Methyl iodide → Methyl 1-methyl-1H-indazole-6-carboxylate

HRID 514397

Reaction equation

HRID 514397 reaction equation
[NH:1]1[C:9]2[C:4](=[CH:5][CH:6]=[C:7]([C:10]([O:12][CH3:13])=[O:11])[CH:8]=2)[CH:3]=[N:2]1.[H-].[Na+].[CH3:16]I>O>[CH3:16][N:1]1[C:9]2[C:4](=[CH:5][CH:6]=[C:7]([C:10]([O:12][CH3:13])=[O:11])[CH:8]=2)[CH:3]=[N:2]1.[CH3:16][N:2]1[CH:3]=[C:4]2[C:9]([CH:8]=[C:7]([C:10]([O:12][CH3:13])=[O:11])[CH:6]=[CH:5]2)=[N:1]1

Participants

6

Reactant 3

HCID 6328Methyl iodideHCID 24758Sodium hydrideHCID 286535methyl 1H-indazole-6-carboxylate

Product 2

HCID 22598983Methyl 1-methyl-1H-indazole-6-carboxylateHCID 37818688Methyl 2-methyl-2H-indazole-6-carboxylate

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

To an ice-cooled solution of methyl 1H-indazole-6-carboxylate (566 mg, 3.21 mmol) was added NaH (154 mg, 3.85 mmol), the mixture was then stirred at room temperature for 30 min. Methyl iodide (547 mg, 3.85 mmol) was added drop wise, and the reaction mixture was stirred overnight. Cooled to 0° C., added water and extracted with ethyl acetate. The organic phase was concentrated and purified by gel chromatograph to provide 130 mg of methyl 1-methyl-1H-indazole-6-carboxylate and 230 mg of methyl 2-methyl-2H-indazole-6-carboxylate, 59%. 1H NMR for methyl 1-methyl-1H-indazole-6-carboxylate: 1H NMR (400 MHz, CDCl3): δ 3.97 (3H, s), 4.14 (3H, s), 7.74-7.82 (2H, m), 8.02 (1H, s), 8.17 (1H, d, J=0.8 Hz). 1H NMR for methyl 2-methyl-2H-indazole-6-carboxylate: 1H NMR (400 MHz, CDCl3): δ 3.94 (3H, s), 4.25 (3H, s), 7.65-7.72 (2H, m), 7.92 (1H, s), 8.47 (1H, d, J=1.2 Hz). [M+H] Calc'd for C10H10N2O2, 191. Found, 191.

Workup

  1. stirringthe reaction mixture was stirred overnight
  2. temperatureCooled to 0° C.
  3. extractionextracted with ethyl acetate
  4. concentrationThe organic phase was concentrated
  5. custompurified by gel chromatograph

Sources & evidence

ORD record
ord-aa3919e6d7b24fa192a385ad983de516
Source dataset
uspto-grants-2015_08
Patent number
US09107916B2

Linked notes

Loading…