Ammonia → 5-amino-2-butyl-1-(2-methylpropyl)-1H-imidazole-4-carbonitrile

HRID 1920251

Reaction equation

HRID 1920251 reaction equation
N.[C:2]1([CH3:12])[CH:7]=[CH:6][C:5](S(O)(=O)=O)=CC=1.[NH2:13][CH:14]([C:17]#[N:18])[C:15]#[N:16].C(OC)(OC)(OC)CCCC.[CH2:30]([NH2:34])[CH:31]([CH3:33])[CH3:32]>C(#N)C>[NH2:16][C:15]1[N:34]([CH2:30][CH:31]([CH3:33])[CH3:32])[C:5]([CH2:6][CH2:7][CH2:2][CH3:12])=[N:13][C:14]=1[C:17]#[N:18]

Participants

6

Reactant 4

HCID 222AmmoniaHCID 6558IsobutylamineHCID 83755Trimethyl orthovalerateHCID 563049Aminomalononitrile p-toluenesulphonate

Product 1

HCID 585001395-amino-2-butyl-1-(2-methylpropyl)-1H-imidazole-4-carbonitrileYield 62.1%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

Dry ammonia was bubbled through a stirred solution of aminomalononitrile p-toluenesulfonate (25.0 g, 98.7 mmol) in anhydrous acetonitrile (1 L). The reaction warmed slightly, and precipitate formed. The precipitate was removed by filtration, and the filtrate was concentrated to a volume of about 500 mL. Trimethyl orthovalerate (17.0 mL, 98.7 mmol) was added, and the resulting solution was heated at reflux for 30 minutes and then allowed to cool to room temperature. Isobutylamine (9.8 mL, 99 mmol) was added, and the reaction was complete in minutes as evidenced by thin layer chromatography (TLC). The volatiles were removed under reduced pressure, and the residue was dissolved in ethyl acetate (400 mL). The resulting solution was washed sequentially with aqueous sodium hydroxide (75 mL of 2 M), water, and brine; dried over magnesium sulfate, and concentrated under reduced pressure to provide a dark solid. The crude product was purified by column chromatography on silica gel (eluting with 50/50 ethyl acetate/hexane) to provide 13.50 g (62%) of 5-amino-2-butyl-1-(2-methylpropyl)-1H-imidazole-4-carbonitrile as a brown solid.

Workup

  1. temperatureThe reaction warmed slightly
  2. customprecipitate formed
  3. customThe precipitate was removed by filtration
  4. concentrationthe filtrate was concentrated to a volume of about 500 mL
  5. temperaturethe resulting solution was heated
  6. temperatureat reflux for 30 minutes
  7. waitthe reaction was complete in minutes
  8. customThe volatiles were removed under reduced pressure
  9. dissolutionthe residue was dissolved in ethyl acetate (400 mL)
  10. washThe resulting solution was washed sequentially with aqueous sodium hydroxide (75 mL of 2 M), water, and brine
  11. dry with materialdried over magnesium sulfate
  12. concentrationconcentrated under reduced pressure
  13. customto provide a dark solid
  14. customThe crude product was purified by column chromatography on silica gel (eluting with 50/50 ethyl acetate/hexane)

Sources & evidence

ORD record
ord-eebb4b29fbff490aa010ed2a23676b60
Source dataset
uspto-grants-2012_05
Patent number
US08168802B2

Linked notes

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