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

HRID 516739Notes

Reaction equation

HRID 516739 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-4714b5308a4243c3946350022cdd74ba
Source dataset
uspto-grants-2015_08
Patent number
US09114141B2

Reaction notes

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