Isobutylamine → 5-amino-1-(2-methylpropyl)-2-propyl-1H-imidazole-4-carbonitrile

HRID 1920259Notes

Reaction equation

HRID 1920259 reaction equation
[C:1]1([CH3:11])[CH:6]=[CH:5]C(S(O)(=O)=O)=CC=1.[NH2:12][CH:13]([C:16]#[N:17])[C:14]#[N:15].C(N(CC)CC)C.C(OC)(OC)(OC)CCC.[CH2:35]([NH2:39])[CH:36]([CH3:38])[CH3:37]>O1CCCC1>[NH2:15][C:14]1[N:39]([CH2:35][CH:36]([CH3:38])[CH3:37])[C:5]([CH2:6][CH2:1][CH3:11])=[N:12][C:13]=1[C:16]#[N:17]

Participants

6

Reactant 4

HCID 6558IsobutylamineHCID 8471Triethylamine2×HCID 1235121,1,1-Trimethoxybutane2×HCID 563049Aminomalononitrile p-toluenesulphonate

Product 1

HCID 585001355-amino-1-(2-methylpropyl)-2-propyl-1H-imidazole-4-carbonitrileYield 70.4%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

Aminomalononitrile p-toluenesulfonate (15.0 g, 59.2 mmol) and triethylamine (9.08 mL, 71.1 mmol) were combined in tetrahydrofuran (THF) (200 mL) and stirred for 30 minutes; the reaction became homogeneous. Trimethyl orthobutyrate (11.4 mL, 71.1 mmol) was added, and the solution was heated at reflux for three hours. An analysis by TLC indicated the presence of starting material, and additional trimethyl orthobutyrate (5.0 mL) was added. The solution was heated at reflux for another 3.5 hours and allowed to cool to room temperature. A mixture of isobutylamine (7.06 mL, 71.1 mmol) and triethylamine (9.08 mL, 71.1 mmol) was added, and the reaction was stirred overnight. The majority of the THF was removed under reduced pressure, and the residue was partitioned between dichloromethane and saturated aqueous sodium bicarbonate. The aqueous layer was extracted twice with dichloromethane. The combined organic fractions were washed with brine, dried over magnesium sulfate, and concentrated under reduced pressure to provide an orange solid that was triturated with ethyl acetate and isolated by filtration to provide 8.60 g (70%) of 5-amino-1-(2-methylpropyl)-2-propyl-1H-imidazole-4-carbonitrile as a white solid.

Workup

  1. temperaturethe solution was heated
  2. temperatureat reflux for three hours
  3. additionwas added
  4. temperatureThe solution was heated
  5. temperatureat reflux for another 3.5 hours
  6. additionwas added
  7. stirringthe reaction was stirred overnight
  8. customThe majority of the THF was removed under reduced pressure
  9. customthe residue was partitioned between dichloromethane and saturated aqueous sodium bicarbonate
  10. extractionThe aqueous layer was extracted twice with dichloromethane
  11. washThe combined organic fractions were washed with brine
  12. dry with materialdried over magnesium sulfate
  13. concentrationconcentrated under reduced pressure
  14. customto provide an orange solid
  15. customthat was triturated with ethyl acetate
  16. customisolated by filtration

Sources & evidence

ORD record
ord-31402c2d62da4bde96c639e6418c5c33
Source dataset
uspto-grants-2012_05
Patent number
US08168802B2

Reaction notes

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