1H-Indazole-5-carbonitrile → 5-(Aminomethyl)-1H-indazole

HRID 842715Notes

Reaction equation

HRID 842715 reaction equation
[H-].[H-].[H-].[H-].[Li+].[Al+3].[C:7]([C:9]1[CH:10]=[C:11]2[C:15](=[CH:16][CH:17]=1)[NH:14][N:13]=[CH:12]2)#[N:8]>C1COCC1>[NH2:8][CH2:7][C:9]1[CH:10]=[C:11]2[C:15](=[CH:16][CH:17]=1)[NH:14][N:13]=[CH:12]2

Participants

4

Reactant 2

HCID 111263841H-Indazole-5-carbonitrileHCID 21226445Aluminium lithium hydride

Product 1

HCID 120962235-(Aminomethyl)-1H-indazole

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
0 °C

Procedure

To a solution-of LiAlH4 (0.76 g, 20.1 mmol) in THF (10 mL) cooled to 0° C. was added a solution of 5-cyanoindazole (0.64 g, 4.47 mmol) in THF (10 mL) dropwise. After 0.5 h the reaction mixture was warmed to reflux for 2 h, then cooled to 0° C. and quenched by the careful addition of water (0.76 mL), 1.0 N sodium hydroxide (0.76 mL), and water (2.28 mL). This mixture was filtered through a pad of celite and washed with THF/MeOH (3:1, 300 mL). Removal of the solvent in vacuo provided a solid which was purified via flash column chromatography (25×150 mm column; elution with MeOH:CH2Cl2:CH2Cl2 saturated with NH3, 10:60:30). This afforded the title compound as a light yellow solid:

Workup

  1. temperatureAfter 0.5 h the reaction mixture was warmed
  2. temperatureto reflux for 2 h
  3. customquenched by the careful addition of water (0.76 mL), 1.0 N sodium hydroxide (0.76 mL), and water (2.28 mL)
  4. filtrationThis mixture was filtered through a pad of celite
  5. washwashed with THF/MeOH (3:1, 300 mL)
  6. customRemoval of the solvent in vacuo
  7. customprovided a solid which
  8. customwas purified via flash column chromatography (25×150 mm column; elution with MeOH:CH2Cl2:CH2Cl2 saturated with NH3, 10:60:30)

Sources & evidence

ORD record
ord-3b570a94bafb476f9cabe83f65de6e29
Source dataset
uspto-grants-2002_04
Patent number
US06376499B1

Reaction notes

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