Dimethylformamide → 4,6-Dimethylpyrimidine-2-carbonitrile

HRID 1025233Notes

Reaction equation

HRID 1025233 reaction equation
Cl[C:2]1[N:7]=[C:6]([CH3:8])[CH:5]=[C:4]([CH3:9])[N:3]=1.[CH3:10][N:11](C=O)C>CCOC(C)=O.[C-]#N.[Zn+2].[C-]#N.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[CH3:9][C:4]1[CH:5]=[C:6]([CH3:8])[N:7]=[C:2]([C:10]#[N:11])[N:3]=1

Participants

6

Reactant 2

HCID 6228DimethylformamideHCID 205502-Chloro-4,6-dimethylpyrimidine

Product 1

HCID 8707424,6-Dimethylpyrimidine-2-carbonitrile

Reagents, catalysts & solvents 3

HCID 11186Zinc cyanide (Zn(CN)2)CatalystHCID 178418397HCID 178418397, compoundCatalystHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
110 °C

Procedure

2-Chloro-4,6-dimethylpyrimidine (3.3 g, 0.023 mol) was combined with zinc cyanide (2.7 g, 0.023 mol, 1 eq.) and tetrakis(triphenylphosphine)palladium (0) (2.7 g, 0.0023 mol, 0.1 eq.) in DMF (20 ml), and the slurry was heated at 110° C. under nitrogen for 0.5 h. The mixture was cooled to room temperature, diluted with EtOAc (70 ml) and washed twice with 2N ammonium hydroxide (50 ml). The EtOAc solution was washed with brine (20 ml) and concentrated in vacuum to provide the crude mixture. The crude was then purified by column chromatography (30% EtOAc/hexane) to afford 4,6-dimethylpyrimidine-2-carbonitrile. Yield: 0.8 g (26%). 1H NMR (400 MHz, CDCl3): δ2.48 (s, 6H), 7.21 (s, 1H). LCMS: (ES+) m/z=133.6 (M)+

Workup

  1. temperatureThe mixture was cooled to room temperature
  2. washwashed twice with 2N ammonium hydroxide (50 ml)
  3. washThe EtOAc solution was washed with brine (20 ml)
  4. concentrationconcentrated in vacuum
  5. customto provide the crude mixture
  6. customThe crude was then purified by column chromatography (30% EtOAc/hexane)

Sources & evidence

ORD record
ord-1ab5c0118d194958890014a5a36cb4ff
Source dataset
uspto-grants-2014_05
Patent number
US08722688B2

Reaction notes

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