Triethylamine → HCID 58500131, compound

HRID 1920270Notes

Reaction equation

HRID 1920270 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.[NH2:35][CH2:36][CH2:37][O:38][CH2:39][CH2:40][NH:41][C:42](=[O:48])[O:43][C:44]([CH3:47])([CH3:46])[CH3:45]>C1COCC1>[NH2:15][C:14]1[N:35]([CH2:36][CH2:37][O:38][CH2:39][CH2:40][NH:41][C:42](=[O:48])[O:43][C:44]([CH3:46])([CH3:45])[CH3:47])[C:5]([CH2:6][CH2:1][CH3:11])=[N:12][C:13]=1[C:16]#[N:17]

Participants

6

Reactant 4

HCID 8471Triethylamine2×HCID 1235121,1,1-Trimethoxybutane2×HCID 563049Aminomalononitrile p-toluenesulphonateHCID 12106198tert-Butyl [2-(2-aminoethoxy)ethyl]carbamate

Product 1

HCID 58500131HCID 58500131, compoundYield 91.5%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
25 °C

Procedure

Under a nitrogen atmosphere, aminomalononitrile p-toluenesulfonate (55.0 g, 0.217 mol) and anhydrous THF (1.1 L) were combined, and triethylamine (23.1 g, 0.228 mol) was added with stirring to the resulting suspension. After the suspension was stirred for 25 minutes; the reaction became homogeneous, and trimethyl orthobutyrate (36.5 mL, 0.228 mol) was added. The solution was heated at reflux for 75 minutes. An analysis by TLC indicated the presence of starting material, and additional trimethyl orthobutyrate (3.5 mL) was added. The solution was heated at reflux for another 15 minutes and allowed to cool to 25° C. Triethylamine (32 mL, 0.29 mol) and tert-butyl 2-(2-aminoethoxy)ethylcarbamate (48.8 g, 0.239 mol) were added, and the reaction was stirred for 18 hours at room temperature. The volatiles were removed under reduced pressure, and the residue was partitioned between dichloromethane (1 L) and saturated aqueous sodium bicarbonate (250 mL). The organic layer was separated and washed sequentially with saturated aqueous sodium carbonate (250 mL) and brine (250 mL), dried over sodium sulfate, filtered, and concentrated under reduced pressure. The residue was combined with material from another run and purified by column chromatography on silica gel (eluting with 20% ethyl acetate in hexane) to provide 67 g (77%) of tert-butyl 2-[2-(5-amino-4-cyano-2-propyl-1H-imidazol-1-yl)ethoxy]ethylcarbamate as an orange semi-solid.

Workup

  1. stirringAfter the suspension was stirred for 25 minutes
  2. temperatureThe solution was heated
  3. temperatureat reflux for 75 minutes
  4. additionwas added
  5. temperatureThe solution was heated
  6. temperatureat reflux for another 15 minutes
  7. stirringthe reaction was stirred for 18 hours at room temperature
  8. customThe volatiles were removed under reduced pressure
  9. customthe residue was partitioned between dichloromethane (1 L) and saturated aqueous sodium bicarbonate (250 mL)
  10. customThe organic layer was separated
  11. washwashed sequentially with saturated aqueous sodium carbonate (250 mL) and brine (250 mL)
  12. dry with materialdried over sodium sulfate
  13. filtrationfiltered
  14. concentrationconcentrated under reduced pressure
  15. custompurified by column chromatography on silica gel (eluting with 20% ethyl acetate in hexane)

Sources & evidence

ORD record
ord-9bc91bdaf5ce42158dd078b3d34b4767
Source dataset
uspto-grants-2012_05
Patent number
US08168802B2

Reaction notes

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