Indole-5-carbonitrile, 3-(2-dimethylaminoethyl)- → 2-(5-(Aminomethyl)-1H-indol-3-yl)-N,N-dimethylethanamine

HRID 2223801Notes

Reaction equation

HRID 2223801 reaction equation
[H-].[Al+3].[Li+].[H-].[H-].[H-].[CH3:7][N:8]([CH3:22])[CH2:9][CH2:10][C:11]1[C:19]2[C:14](=[CH:15][CH:16]=[C:17]([C:20]#[N:21])[CH:18]=2)[NH:13][CH:12]=1>>[NH2:21][CH2:20][C:17]1[CH:18]=[C:19]2[C:14](=[CH:15][CH:16]=1)[NH:13][CH:12]=[C:11]2[CH2:10][CH2:9][N:8]([CH3:7])[CH3:22]

Participants

3

Reactant 2

HCID 28511Indole-5-carbonitrile, 3-(2-dimethylaminoethyl)-HCID 21226445Aluminium lithium hydride

Product 1

HCID 574744522-(5-(Aminomethyl)-1H-indol-3-yl)-N,N-dimethylethanamine

Procedure

Lithium aluminium hydride (40.0 mg, 1.055 mmol, 1.5 equivalents) was placed in an argon purged oven dried flask fitted with a stirbar and condenser. Anhydrous diethylether (5 mL) was added and stirring begun. 3-(2-Dimethylamino-ethyl)-1H-indole-5-carbonitrile (57) (150.0 mg, 0.703 mmol, 1.0 equivalent) was dissolved in a separate dry flask in a mixture of anhydrous diethylether (5 mL) and anhydrous tetrahydrofuran (5 mL) and this solution added dropwise to the solution of lithium aluminium hydride and the resulting mixture heated to reflux. After 30 minutes the reaction was cooled to room temperature and quenched with distilled water (50 μL), aqueous 3N sodium hydroxide solution (75 μL) and distilled water (150 μL) sequentially. The solution was filtered and concentrated. The residue was purified via silica gel column chromatography (10-15-20% 2M NH3 in methanol/90-85-80% dichloromethane) to provide 2-(5-(aminomethyl)-1H-indol-3-yl)-N,N-dimethylethanamine (58) as a pale yellow residue (73 mg, 47.8% yield). 1H NMR (DMSO) δ: 2.21 (s, 6H), 2.53 (m, 2H), 2.78 (t, 2H), 3.79 (s, 2H), 7.02-7.05 (d, 1H), 7.09 (s, 1H), 7.24 (d, 1H), 7.44 (s, 1H), 10.66 (br s, 1H). MS: 218 (M+1), 201 (M+1—NH3).

Workup

  1. customdried flask
  2. customfitted with a stirbar and condenser
  3. additionAnhydrous diethylether (5 mL) was added
  4. customdry flask
  5. additionin a mixture of anhydrous diethylether (5 mL) and anhydrous tetrahydrofuran (5 mL)
  6. additionthis solution added dropwise to the solution of lithium aluminium hydride
  7. temperaturethe resulting mixture heated to reflux
  8. customquenched with distilled water (50 μL), aqueous 3N sodium hydroxide solution (75 μL)
  9. distillationdistilled water (150 μL) sequentially
  10. filtrationThe solution was filtered
  11. concentrationconcentrated
  12. customThe residue was purified via silica gel column chromatography (10-15-20% 2M NH3 in methanol/90-85-80% dichloromethane)

Sources & evidence

ORD record
ord-027d16dcaf794d0096cc8bb856d10805
Source dataset
uspto-grants-2008_05
Patent number
US07375219B2

Reaction notes

Loading…