Ethyl Acetate → 5-Aminopyrazine-2-carbonitrile

HRID 1827864Notes

Reaction equation

HRID 1827864 reaction equation
Br[C:2]1[N:3]=[CH:4][C:5]([NH2:8])=[N:6][CH:7]=1.[C-:9]#[N:10].[K+].C(OCC)(=O)C>CN(C)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>[NH2:8][C:5]1[N:6]=[CH:7][C:2]([C:9]#[N:10])=[N:3][CH:4]=1

Participants

8

Reactant 3

HCID 8857Ethyl AcetateHCID 9032Potassium CyanideHCID 5995392-Amino-5-bromopyrazine

Product 1

HCID 139252945-Aminopyrazine-2-carbonitrileYield 94.4%

Reagents, catalysts & solvents 4

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

Procedure

A mixture of Example 1A (19.29 g, 105 mmol), freshly powdered KCN (16.9 g, 260 mmol), CuI (49.5 g, 260 mmol), 18-crown-6 (2.08 g, 7.8 mmol), and (PPh3)4Pd (1.8 g, 1.57 mmol) in N,N-dimethylformamide (600 mL) was stirred at room temperature for 30 minutes and heated to reflux in an oil bath preheated to about 200° C. The solution was stirred at reflux for 3 hours, cooled to room temperature, poured into ethyl acetate (1 L), filtered through diatomaceous earth (Celite®), treated with silica gel (100 g), and concentrated. The concentrate was purified by flash column chromatography on silica gel with 60% ethyl acetate/hexanes to provide 11.9 g (94.4%) of the desired product. MS (APCI(+)) m/z 121 (M+H)+; 1H NMR (300 MHz, DMSO-d6) δ 8.40 (d, J=0.7 Hz, 1H), 7.90 (d, J=0.7 Hz, 1H), 7.47–7.69 (br s, 2H).

Workup

  1. temperatureheated
  2. temperatureto reflux in an oil bath
  3. custompreheated to about 200° C
  4. temperatureat reflux for 3 hours
  5. filtrationfiltered through diatomaceous earth (Celite®)
  6. additiontreated with silica gel (100 g)
  7. concentrationconcentrated
  8. customThe concentrate was purified by flash column chromatography on silica gel with 60% ethyl acetate/hexanes

Sources & evidence

ORD record
ord-f208c1f0bf93419cbb74dbefd2833d24
Source dataset
uspto-grants-2006_06
Patent number
US07056925B2

Reaction notes

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