Dimethylformamide → 2-Amino-4-chloro-6-methyl-5-pyrimidinecarbonitrile

HRID 243151Notes

Reaction equation

HRID 243151 reaction equation
[Cl:1][C:2]1[C:7](I)=[C:6]([CH3:9])[N:5]=[C:4]([NH2:10])[N:3]=1.[CH3:11][N:12](C=O)C>[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>[NH2:10][C:4]1[N:3]=[C:2]([Cl:1])[C:7]([C:11]#[N:12])=[C:6]([CH3:9])[N:5]=1

Participants

5

Reactant 2

HCID 6228DimethylformamideHCID 116447204-Chloro-5-iodo-6-methylpyrimidin-2-amine

Product 1

HCID 754124462-Amino-4-chloro-6-methyl-5-pyrimidinecarbonitrileYield 5%

Reagents, catalysts & solvents 2

HCID 11186Zinc cyanide (Zn(CN)2)CatalystHCID 178418397HCID 178418397, compoundCatalyst

Conditions

Temperature
140 °C

Procedure

A mixture of 4-chloro-5-iodo-6-methylpyrimidin-2-ylamine (1.35 g, 5.0 mmol), zinc cyanide (288 mg, 2.45 mmol) and tetrakis(triphenylphosphine)palladium (290 mg, 5 mol %) in DMF (20 mL) was purged with argon gas and heated at 140° C., for 15 min, by microwave irradiation. After cooling to RT, the residue was partitioned between EtOAc and water. The aqueous phase was further extracted with EtOAc and the combined organic fractions washed with brine, dried (Na2SO4) and concentrated in vacuo. The resulting residue was purified by column chromatography (Si—PCC, gradient 0-30% EtOAc in DCM) followed by further column chromatography (Si—PCC, gradient 0-7% MeOH in DCM) to afford the title compound (40 mg, 5%) as a pale yellow solid. LCMS (Method C): RT 2.23 min [M+H]+ 169.00. 1H NMR (DMSO-d6, 400 MHz): δ 8.11 (2H, br s), 2.42 (3H, s)

Workup

  1. customwas purged with argon gas
  2. temperatureAfter cooling to RT
  3. customthe residue was partitioned between EtOAc and water
  4. extractionThe aqueous phase was further extracted with EtOAc
  5. washthe combined organic fractions washed with brine
  6. dry with materialdried (Na2SO4)
  7. concentrationconcentrated in vacuo
  8. customThe resulting residue was purified by column chromatography (Si—PCC, gradient 0-30% EtOAc in DCM)

Sources & evidence

ORD record
ord-e290e1c6e97549109d4512a6bc89c9d7
Source dataset
uspto-grants-2014_02
Patent number
US08653089B2

Reaction notes

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