Methyl iodide → 6-Amino-4-methoxy-2-methylnicotinonitrile

HRID 928387Notes

Reaction equation

HRID 928387 reaction equation
[NH2:1][C:2]1[N:7]=[C:6]([CH3:8])[C:5]([C:9]#[N:10])=[C:4]([O-:11])[CH:3]=1.[Na+].[C:13]([O-])([O-])=O.[K+].[K+].CI.C([O-])(O)=O.[Na+]>CN(C=O)C>[NH2:1][C:2]1[CH:3]=[C:4]([O:11][CH3:13])[C:5]([C:9]#[N:10])=[C:6]([CH3:8])[N:7]=1

Participants

6

Reactant 4

HCID 6328Methyl iodideHCID 11430Potassium CarbonateHCID 516892Sodium BicarbonateHCID 58081220Sodium 6-amino-3-cyano-2-methylpyridin-4-olate

Product 1

HCID 667237286-Amino-4-methoxy-2-methylnicotinonitrile

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a mixture of sodium 6-amino-3-cyano-2-methylpyridin-4-olate (500 mg, 2.92 mmol, prepared in analogy to WO2001062233A2 and isolated as sodium salt), and K2CO3 (808 mg, 5.84 mmol) in DMF (1 ml) was added MeI (0.200 ml, 3.21 mmol), and the reaction mixture was stirred at it for 9 d. Saturated NaHCO3 (50 ml) was added and the mixture was extracted with EA (4×20 ml). The combined organic extracts were diluted with additional DCM and MeOH until homogeneous, dried over Na2SO4, filtered and concentrated. The crude product was recrystallized from refluxing MeOH-DCM to afford the title compound. 1H-NMR (DMSO-d6, 400 MHz): 2.34 (s, 3H), 3.82 (s, 3H), 5.91 (s, 1H), 6.83 (br, s, 2H); LCMS RtM=1.11 min, [M+H]+=164.2.

Workup

  1. extractionthe mixture was extracted with EA (4×20 ml)
  2. additionThe combined organic extracts were diluted with additional DCM and MeOH until homogeneous,
  3. dry with materialdried over Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe crude product was recrystallized
  7. temperaturefrom refluxing MeOH-DCM

Sources & evidence

ORD record
ord-a063049e807e44a6947682d2b269d4ee
Source dataset
uspto-grants-2016_03
Patent number
US09290485B2

Reaction notes

Loading…