Succinic anhydride → HCID 89437178, compound

HRID 593204Notes

Reaction equation

HRID 593204 reaction equation
[NH2:1][C:2]1[N:3]=[CH:4][C:5]([C:8]#[N:9])=[N:6][CH:7]=1.[C:10]1(=[O:16])[O:15][C:13](=[O:14])[CH2:12][CH2:11]1>O1CCCC1>[C:8]([C:5]1[N:6]=[CH:7][C:2]([NH:1][C:10](=[O:16])[CH2:11][CH2:12][C:13]([OH:15])=[O:14])=[N:3][CH:4]=1)#[N:9]

Participants

4

Reactant 2

HCID 7922Succinic anhydride2×HCID 139252945-Aminopyrazine-2-carbonitrile

Product 1

HCID 89437178HCID 89437178, compoundYield 71%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

The 5-aminopyrazine-2-carbonitrile (commercially available, 1.0 g, 8.32 mmol) was dissolved in tetrahydrofuran then succinic anhydride (1.04 g, 10.4 mmol) was added, the mixture was stirred at room temperature for 2 h and at reflux overnight. Then 1.0 equivalent of succinic anhydride was added and the solution was refluxed for 4 days. The reaction was stopped and the solution was partitioned between ethyl acetate and water. The aqueous layer was separated, acidified and extracted with ethyl acetate (3×). The combined organic layer was dried on magnesium sulfate and concentrated under vacuum. The residue was purified by flash chromatography eluting with cyclohexane-ethyl acetate (1/3) with acid acetic (1%) to give 4-[(5-cyanopyrazin-2-yl)amino]-4-oxo-butanoic acid A1 (1.30 g, 71%). M.p.=201-202° C., 1H NMR (400 MHz, DMSO-d6) δ 12.09 (bs, 1H), 11.40 (s, 1H), 9.41 (s, 1H), 8.96 (s, 1H), 2.73 (t, 2H), 2.55 (t, 2H) ppm. LC-MS (Method B): RT 0.96, 219 (M−H+)

Workup

  1. temperatureat reflux overnight
  2. temperaturethe solution was refluxed for 4 days
  3. customthe solution was partitioned between ethyl acetate and water
  4. customThe aqueous layer was separated
  5. extractionextracted with ethyl acetate (3×)
  6. customThe combined organic layer was dried on magnesium sulfate
  7. concentrationconcentrated under vacuum
  8. customThe residue was purified by flash chromatography
  9. washeluting with cyclohexane-ethyl acetate (1/3) with acid acetic (1%)

Sources & evidence

ORD record
ord-9f8d38130dc3460cb032bffbd6779a46
Source dataset
uspto-grants-2016_01
Patent number
US09241489B2

Reaction notes

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