Dimethylformamide → 2-Amino-6-methoxypyrimidine-4-carbonitrile

HRID 2071017Notes

Reaction equation

HRID 2071017 reaction equation
Cl[C:2]1[CH:7]=[C:6]([O:8][CH3:9])[N:5]=[C:4]([N:10](C)C)[N:3]=1.[CH3:13][N:14](C=O)C>CCOCC.[NH4+].[OH-].[C-]#N.[C-]#N.[Zn+2].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>[NH2:10][C:4]1[N:3]=[C:2]([C:13]#[N:14])[CH:7]=[C:6]([O:8][CH3:9])[N:5]=1

Participants

7

Reactant 2

HCID 6228DimethylformamideHCID 7375984-chloro-6-methoxy-N,N-dimethylpyrimidin-2-amine

Product 1

HCID 141292502-Amino-6-methoxypyrimidine-4-carbonitrileYield 65%

Reagents, catalysts & solvents 4

HCID 11186Zinc cyanide (Zn(CN)2)CatalystHCID 178418397HCID 178418397, compoundCatalystHCID 3283Diethyl EtherSolventHCID 14923Ammonium HydroxideSolvent

Conditions

Temperature
95 °C

Procedure

A solution of 4-chloro-6-methoxy-N,N-dimethylpyrimidin-2-amine (0.350 g, 2.19 mmol, 1 eq) in 10 ml anhydrous DMF was degassed with Ar for 5 min. Zn(CN)2 (0.155 g, 1.32 mmol, 0.6 eq) and Pd(PPh3)4 (0.253 g, 0.219 mmol, 10 mol %) were added and the mixture was heated to 95° C. After 23 h the reaction was cooled to room temperature and the mixture was diluted with Et2O and NH4OH (28%). After stirring for 1 h the layers were separated. The organic layer was washed with water (×3), brine (×1), and dried over Na2SO4. The inorganics were filtered off, and the solvent was removed in vacuo. Purification via flash chromatography yielded 0.214 g (1.43 mmol, 65% yield) of 2-amino-6-methoxypyrimidine-4-carbonitrile.

Workup

  1. temperatureAfter 23 h the reaction was cooled to room temperature
  2. customwere separated
  3. washThe organic layer was washed with water (×3), brine (×1)
  4. dry with materialdried over Na2SO4
  5. filtrationThe inorganics were filtered off
  6. customthe solvent was removed in vacuo
  7. customPurification via flash chromatography

Sources & evidence

ORD record
ord-7aa6d7821cbc405f8d5cfa237e825001
Source dataset
uspto-grants-2012_10
Patent number
US08299267B2

Reaction notes

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