Potassium Cyanide → 5-Amino-3-chloropyrazine-2-carbonitrile

HRID 40657Notes

Reaction equation

HRID 40657 reaction equation
Br[C:2]1[N:3]=[CH:4][C:5]([NH2:9])=[N:6][C:7]=1[Cl:8].[C-:10]#[N:11].[K+]>CN(C=O)C.CCOC(C)=O.[Cu]I.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.C1OCCOCCOCCOCCOCCOC1>[NH2:9][C:5]1[N:6]=[C:7]([Cl:8])[C:2]([C:10]#[N:11])=[N:3][CH:4]=1

Participants

8

Reactant 2

HCID 9032Potassium CyanideHCID 181802075-Bromo-6-chloropyrazin-2-amine

Product 1

HCID 210753925-Amino-3-chloropyrazine-2-carbonitrileYield 82%

Reagents, catalysts & solvents 5

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 2855718-Crown-6CatalystHCID 178418397HCID 178418397, compoundCatalystHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

A mixture of 5-bromo-6-chloropyrazin-2-amine (1.00 g, 4.8 mmol), copper (I) iodide (914 mg, 4.8 mmol), 18-crown-6 (95 mg, 0.36 mmol) and tetrakis(triphenylphosphine)palladium (0) (83 mg, 0.072 mmol) was suspended in dry DMF (20 mL) and a stream of nitrogen was passed through it for 5 minutes. Potassium cyanide (312 mg, 4.8 mmol) was added and the mixture was stirred at room temperature for 30 minutes, then refluxed at 200° C. for 3 hours. The mixture was cooled and diluted with EtOAc and absorbed onto silica gel (10 g). DMF was removed by evaporation in a Genevac evaporator. The product was purified by flash chromatography, eluting with 1:1 ethyl acetate-hexane, to yield the title compound as a yellow solid (607 mg, 3.93 mmol, 82%). 1H NMR (d6-DMSO, 400 MHz) δ 8.1 (br s, 2H), 7.87 (s, 1H). LC-MS (1) Rt=1.20 min; m/z (ESI−) 153 (M−H).

Workup

  1. temperaturerefluxed at 200° C. for 3 hours
  2. temperatureThe mixture was cooled
  3. customabsorbed onto silica gel (10 g)
  4. customDMF was removed by evaporation in a Genevac evaporator
  5. customThe product was purified by flash chromatography
  6. washeluting with 1:1 ethyl acetate-hexane

Sources & evidence

ORD record
ord-81cf38f6865a4f74b880efbc5a0b5308
Source dataset
uspto-grants-2013_09
Patent number
US08530468B2

Reaction notes

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