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

HRID 1920261Notes

Reaction equation

HRID 1920261 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].C(=O)([O-])[O-].[Na+].[Na+]>C1(C)C=CC=CC=1.C(OC)(OC)(OC)CCC.O>[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

9

Reactant 5

HCID 6558IsobutylamineHCID 8471Triethylamine2×HCID 10340Sodium CarbonateHCID 1235121,1,1-TrimethoxybutaneHCID 563049Aminomalononitrile p-toluenesulphonate

Product 1

HCID 585001355-amino-1-(2-methylpropyl)-2-propyl-1H-imidazole-4-carbonitrileYield 65%

Reagents, catalysts & solvents 3

HCID 1235121,1,1-TrimethoxybutaneCatalystHCID 962WaterSolventHCID 1140TolueneSolvent

Conditions

Temperature
60 °C

Procedure

Aminomalononitrile p-toluenesulfonate (744.65 g, 2.94 mol), triethylamine (297.5 g, 2.94 mol), and trimethyl orthobutyrate (436 g, 2.94 mol) were combined in toluene (7.45 L) and the solution was heated at 60° C. for 2.5 hours. Additional trimethyl orthobutyrate (21 g) was added, and the reaction was allowed to cool over a period of 30 minutes, and triethylamine (297.5 g, 2.94 mol) was added. The solution was further cooled to about 3° C. over 30 minutes, and isobutylamine (215.03 g, 2.94 mol) was added over a period of 90 minutes. During the addition, the reaction temperature rose to 10° C. The reaction was warmed to room temperature slowly and stirred overnight. Deionized water (7.35 L) and sodium carbonate (735 g) were added over a period of 15 minutes while maintaining the temperature of the mixture at 20° C. with the addition of ice. The mixture was stirred for 15 minutes, and then the precipitate was isolated by filtration, washed sequentially with toluene (300 mL) and water (3 L), air-dried, and further dried under vacuum at 70° C. for 24 hours to provide 394.4 g (65%) of 5-amino-1-(2-methylpropyl)-2-propyl-1H-imidazole-4-carbonitrile as a beige solid, mp 134.5-136.5° C.

Workup

  1. temperatureto cool over a period of 30 minutes
  2. temperatureThe solution was further cooled to about 3° C. over 30 minutes
  3. additionDuring the addition
  4. customrose to 10° C
  5. temperatureThe reaction was warmed to room temperature slowly
  6. temperaturewhile maintaining the temperature of the mixture at 20° C.
  7. additionwith the addition of ice
  8. stirringThe mixture was stirred for 15 minutes
  9. customthe precipitate was isolated by filtration
  10. washwashed sequentially with toluene (300 mL) and water (3 L)
  11. customair-dried
  12. customfurther dried under vacuum at 70° C. for 24 hours

Sources & evidence

ORD record
ord-3206c3be49e04bb4880decaaa8ba85cf
Source dataset
uspto-grants-2012_05
Patent number
US08168802B2

Reaction notes

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