3-Methyl-1H-indole-5-carbonitrile → (3-methyl-1H-indol-5-yl)methanamine

HRID 475253Notes

Reaction equation

HRID 475253 reaction equation
[CH3:1][C:2]1[C:10]2[C:5](=[CH:6][CH:7]=[C:8]([C:11]#[N:12])[CH:9]=2)[NH:4][CH:3]=1>[Ni].N.CO>[CH3:1][C:2]1[C:10]2[C:5](=[CH:6][CH:7]=[C:8]([CH2:11][NH2:12])[CH:9]=2)[NH:4][CH:3]=1

Participants

5

Reactant 1

HCID 574751293-Methyl-1H-indole-5-carbonitrile

Product 1

HCID 18470813(3-methyl-1H-indol-5-yl)methanamineYield 97%

Reagents, catalysts & solvents 3

HCID 935NickelCatalystHCID 222AmmoniaSolventHCID 887MethanolSolvent

Procedure

Raney Nickel (wet, 1.0 g) was added to a stirred solution of 192 (220.0 mg, 1.41 mmol) in 2.0 M ammonia in MeOH (10 mL). The reaction mixture was hydrogenated under an H2 balloon at 1 atmospheric pressure at RT for 3 d. The reaction mixture was filtered through a pad of Celite® and the pad was rinsed well with MeOH and water. Volatile solvent from the filtrate was removed in vacuo. The aqueous phase from filtrate was thrice extracted with EtOAc. The combined organic extracts were dried (Na2SO4), filtered and concentrated in vacuo. Crystallization from DCM/heptane afforded 219.1 mg (97%) of (3-methyl-1H-indol-5-yl)methanamine (194) as a white solid: 1H NMR (400 MHz, CDCl3): δ 7.87 (br s, 1H), 7.49 (s, 1H), 7.29 (d, J=8.3 Hz, 1H), 7.12 (d, J=8.3 Hz, 1H), 6.95 (s, 1H), 3.95 (s, 2H), 2.31 (s, 3H), 1.59 (br s, 2H).

Workup

  1. customat RT
  2. customfor 3 d
  3. filtrationThe reaction mixture was filtered through a pad of Celite®
  4. washthe pad was rinsed well with MeOH and water
  5. customVolatile solvent from the filtrate was removed in vacuo
  6. extractionextracted with EtOAc
  7. dry with materialThe combined organic extracts were dried (Na2SO4)
  8. filtrationfiltered
  9. concentrationconcentrated in vacuo
  10. customCrystallization from DCM/heptane

Sources & evidence

ORD record
ord-4ef38500e77c41a7ba8fae666a357bba
Source dataset
uspto-grants-2014_01
Patent number
US08637537B2

Reaction notes

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