Triethylamine → 4-Methylpyrimidine-2-carbonitrile

HRID 1889035Notes

Reaction equation

HRID 1889035 reaction equation
Cl[C:2]1[N:7]=[C:6]([CH3:8])[CH:5]=[CH:4][N:3]=1.[CH2:9]([N:11](CC)CC)C.[C-]#N.[K+]>CN(C)C=O.ClCCl.[Pd](Cl)Cl.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>[CH3:8][C:6]1[CH:5]=[CH:4][N:3]=[C:2]([C:9]#[N:11])[N:7]=1

Participants

7

Reactant 3

HCID 8471TriethylamineHCID 9032Potassium Cyanide2×HCID 116296072-Chloro-4-methylpyrimidine

Product 1

HCID 126843244-Methylpyrimidine-2-carbonitrile

Reagents, catalysts & solvents 3

HCID 6102075Dichlorobis(triphenylphosphine)palladiumCatalystHCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
80 °C

Procedure

2-Chloro-4-methylpyrimidine (0.5 g, 3.89 mmol) was dissolved in N,N-dimethyl formamide (DMF) (60.8 ml) and triethylamine (0.813 ml, 5.83 mmol) and potassium cyanide (0.507 g, 7.78 mmol) were added. The solution was sonicated till most of the potassium cyanide had gone into solution then bis(triphenylphosphine) palladium(II) chloride (0.273 g, 0.389 mmol) was added. The solution was heated to 80° C. and left to stir over the weekend. LCMS showed that the product had formed. The reaction mixture was diluted in dichloromethane and washed with saturated ammonium chloride, water and brine. The organic extracts were dried over magnesium sulfate and the solvent was removed under reduced pressure. This afforded a crude of 1.129 g, which was purified by flash chromatography (Biotage Isolera 4, 100 g cartridge) with a gradient of dichloromethane 0-100% in iso-hexane. The solvent was removed under reduced pressure to afford the desired product in 0.199 g.

Workup

  1. waitleft
  2. customhad formed
  3. washwashed with saturated ammonium chloride, water and brine
  4. dry with materialThe organic extracts were dried over magnesium sulfate
  5. customthe solvent was removed under reduced pressure
  6. customThis afforded a crude of 1.129 g, which
  7. customwas purified by flash chromatography (Biotage Isolera 4, 100 g cartridge) with a gradient of dichloromethane 0-100% in iso-hexane
  8. customThe solvent was removed under reduced pressure

Sources & evidence

ORD record
ord-bb65a59dea8e4902844f1c12164171f1
Source dataset
uspto-grants-2013_08
Patent number
US08501946B2

Reaction notes

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