Ammonia → 3-(Aminomethyl)-6-methyl-4-propylpyridin-2(1H)-oneacetate

HRID 85530Notes

Reaction equation

HRID 85530 reaction equation
[CH3:1][C:2]1[NH:7][C:6](=[O:8])[C:5]([C:9]#[N:10])=[C:4]([CH2:11][CH2:12][CH3:13])[CH:3]=1.N>CO.[Ni]>[NH2:10][CH2:9][C:5]1[C:6](=[O:8])[NH:7][C:2]([CH3:1])=[CH:3][C:4]=1[CH2:11][CH2:12][CH3:13]

Participants

5

Reactant 2

HCID 222AmmoniaHCID 156418016-Methyl-2-oxo-4-propyl-1,2-dihydropyridine-3-carbonitrile

Product 1

HCID 671241403-(Aminomethyl)-6-methyl-4-propylpyridin-2(1H)-oneacetate

Reagents, catalysts & solvents 2

HCID 935NickelCatalystHCID 887MethanolSolvent

Procedure

To a suspension of Raney Ni (2 g) in methanol (250 mL) was added 1,2-dihydro-6-methyl-2-oxo-4-propylpyridine-3-carbonitrile (5 g, 28.4 mmol) and methanolic ammonia (750 mL). The reaction mixture was stirred at room temperature under hydrogen pressure (60 psi) for 48 hrs. The reaction mixture was filtered through celite pad and washed with methanol (250 mL). The filtrate was concentrated under reduced pressure to afford the crude product (5.1 g). The crude product was purified by column chromatography by using a short column of silica gel (60-120 mesh) treated with methanolic NH3, (eluant: 0-25% methanol in DCM) and isolated to afford the desired product 3-(amino methyl)-6-methyl-4-propylpyridin-2(1H)-one as an off white solid (2 g, 39% yield). 1H NMR (DMSO, 400 MHz): δ 0.921 (t, 3H, J=7.2 Hz), 1.518 (m, 2H), 2.09 (s, 3H), 2.418 (t, 2H, J=7.6 Hz), 3.451 (s, 2H), 4-5.6 (br s, 2H, exchangeable), 5.822 (s, 1H). LCMS E-S (M+H)=181.22.

Workup

  1. filtrationThe reaction mixture was filtered through celite pad
  2. washwashed with methanol (250 mL)
  3. concentrationThe filtrate was concentrated under reduced pressure
  4. customto afford the crude product (5.1 g)
  5. customThe crude product was purified by column chromatography
  6. additiontreated with methanolic NH3, (eluant: 0-25% methanol in DCM)
  7. customisolated

Sources & evidence

ORD record
ord-5ea8bbc4587248c7be1541e6fb0c0e61
Source dataset
uspto-grants-2014_09
Patent number
US08846935B2

Reaction notes

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