2-Methyl-4-methoxymethyl-5-cyano-6-oxypyridine → 3-(aminomethyl)-4-(methoxymethyl)-6-methyl-2(1H)-Pyridinone

HRID 593860Notes

Reaction equation

HRID 593860 reaction equation
[CH3:1][C:2]1[NH:7][C:6](=[O:8])[C:5]([C:9]#[N:10])=[C:4]([CH2:11][O:12][CH3:13])[CH:3]=1>C(O)(=O)C.[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][O:12][CH3:13]

Participants

4

Reactant 1

HCID 949992-Methyl-4-methoxymethyl-5-cyano-6-oxypyridine

Product 1

HCID 552557633-(aminomethyl)-4-(methoxymethyl)-6-methyl-2(1H)-Pyridinone

Reagents, catalysts & solvents 2

HCID 935NickelCatalystHCID 176Acetic AcidSolvent

Procedure

6-Methyl-4-[(methyloxy)methyl]-2-oxo-1,2-dihydro-3-pyridinecarbonitrile (1.000 g, 5.61 mmol) was suspended in acetic acid (150 ml) and the solution passed through an H-cube instrument equipped with Raney-Ni cartridge at a rate of 1 mL/min at 50 psi and 60° C. After 18 h. the acetic acid was removed under reduced pressure and the remaining residue was dissolved in MeOH. The methanolic solution was passed through a 0.2 μm teflon syringe filter. The methanolic filtrate was purified by reverse phase HPLC (Gemini 50×100 5 μm column. Run 1: 3 min, 90-10%. Run 2, 5 min 0-10%. Run 3, 10 min, 0-20%. The product fractions were concentrated to dryness on a Genevac HT-4 instrument to afford 3-(aminomethyl)-6-methyl-4-[(methyloxy)methyl]-2(1H)-pyridinone as a pale grey waxy solid (900 mg, 70.2% yield) LCMS MH+=183.0 1H NMR (400 MHz, DMSO-d6) δ 8.40 (br. s., 1H), 6.10 (s, 1H), 4.39 (s, 2H), 3.66 (br. s., 2H), 3.32 (s, 3H), 2.19 (s, 3H).

Workup

  1. customAfter 18 h. the acetic acid was removed under reduced pressure
  2. dissolutionthe remaining residue was dissolved in MeOH
  3. filtrationfilter
  4. customThe methanolic filtrate was purified by reverse phase HPLC (Gemini 50×100 5 μm column
  5. custom3 min, 90-10%
  6. custom2, 5 min 0-10%
  7. custom3, 10 min, 0-20%
  8. concentrationThe product fractions were concentrated to dryness on a Genevac HT-4 instrument

Sources & evidence

ORD record
ord-92f92b922eba4ac1aa9c761f8dc01068
Source dataset
uspto-grants-2016_01
Patent number
US09242962B2

Reaction notes

Loading…