Ammonia → 3-(aminomethyl)-4-(sec-butyl)-6-methylpyridin-2(1H)-one

HRID 1476510Notes

Reaction equation

HRID 1476510 reaction equation
[CH:1]([C:5]1[CH:10]=[C:9]([CH3:11])[NH:8][C:7](=[O:12])[C:6]=1[C:13]#[N:14])([CH2:3][CH3:4])[CH3:2].N>CO.[Ni]>[CH:1]([C:5]1[CH:10]=[C:9]([CH3:11])[NH:8][C:7](=[O:12])[C:6]=1[CH2:13][NH2:14])([CH2:3][CH3:4])[CH3:2]

Participants

5

Reactant 2

HCID 222AmmoniaHCID 682102564-Sec-butyl-1,2-dihydro-6-methyl-2-oxopyridine-3-carbonitrile

Product 1

HCID 674678593-(aminomethyl)-4-(sec-butyl)-6-methylpyridin-2(1H)-oneYield 49%

Reagents, catalysts & solvents 2

HCID 935NickelCatalystHCID 887MethanolSolvent

Procedure

To a suspension of Raney Ni (10 g) in methanol (50 mL) was added 4-sec-butyl-1,2-dihydro-6-methyl-2-oxopyridine-3-carbonitrile (7 g, 36.8 mmol) followed by methanolic ammonia (200 mL) and the resulting reaction mixture was stirred at room temperature under hydrogen pressure (80 psi) for 18 h. 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 (7 g). The reaction was repeated again under same condition. The crude products were combined and purified by silica gel chromatography (eluent: 8% MeOH in CHCl3, spiked with NH3) and the obtained solid was triturated with diethyl ether (50 mL) and dried under vacuum to afford the title compound as yellow solid (3.5 g, 28%). 1H NMR (DMSO-d6, 400 MHz): δ 0.809-0.774 (t, 3H, J=6.8 Hz), 1.113-1.097 (d, 3H, J=6.4 Hz), 1.504-1.468 (t, 2H, J=7.2 Hz), 2.184 (s, 3H), 2.839-2.822 (d, 1H, J=6.8 Hz), 3.822 (s, 2H), 6.059 (s, 1H), 8.315 (bs, 2H); LCMS (ES+) m/z=195.22 (M+H)

Workup

  1. customthe resulting reaction mixture
  2. filtrationThe reaction mixture was filtered through Celite pad
  3. washwashed with methanol (250 mL)
  4. concentrationThe filtrate was concentrated under reduced pressure
  5. customto afford the crude product (7 g)
  6. custompurified by silica gel chromatography (eluent: 8% MeOH in CHCl3, spiked with NH3)
  7. customthe obtained solid was triturated with diethyl ether (50 mL)
  8. customdried under vacuum

Sources & evidence

ORD record
ord-12a235ce30974657bd6bcf4b723717f7
Source dataset
uspto-grants-2015_04
Patent number
US09018382B2

Reaction notes

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