Hydrochloric Acid → 2-n-Propyl-5-(2-methyl-propionylamino)-imidazo[4,5-b]pyridine

HRID 440585Notes

Reaction equation

HRID 440585 reaction equation
[CH2:1]([C:4]1[NH:5][C:6]2[C:7]([N:13]=1)=[N:8][C:9]([NH2:12])=[CH:10][CH:11]=2)[CH2:2][CH3:3].[C:14](Cl)(=[O:18])[CH:15]([CH3:17])[CH3:16].C(N(CC)CC)C.Cl.C(=O)([O-])O.[Na+]>C(Cl)Cl>[CH2:1]([C:4]1[NH:5][C:6]2[C:7]([N:13]=1)=[N:8][C:9]([NH:12][C:14](=[O:18])[CH:15]([CH3:17])[CH3:16])=[CH:10][CH:11]=2)[CH2:2][CH3:3]

Participants

7

Reactant 5

HCID 313Hydrochloric AcidHCID 8471TriethylamineHCID 62325Isobutyryl chlorideHCID 516892Sodium BicarbonateHCID 224075845-Amino-2-propylimidazo[4,5-b]pyridine

Product 1

HCID 224074332-n-Propyl-5-(2-methyl-propionylamino)-imidazo[4,5-b]pyridine

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

2.62 g (15 mMol) of 2-n-propyl-5-amino-imidazo[4,5-b]pyridine are suspended in 100 ml of absolute methylene chloride and 3.16 g (30 mMol) of isobutyric acid chloride are added, with stirring and cooling with ice. Then, at -5° C., a solution of 3.03 g (30 mMol) of triethylamine in 5 ml of methylene chloride is added dropwise. After one hour at ambient temperature the reaction mixture is combined with 100 ml of 2N hydrochloric acid and the mixture is stirred for a further hour. Then the solution is poured onto ice water and mixed with saturated sodium hydrogen carbonate solution. The aqueous phase is extracted 3 times with 100 ml of ethyl acetate, the combined organic phases are then washed with saline solution, dried over sodium sulphate and concentrated by evaporation. The crude product is taken up in methylene chloride and purified over a silica gel column (particle size 0.063-0.2 mm), using as eluant methylene chloride to begin with, followed by mixtures of methylene chloride and ethanol of increasing polarity (25:1 and 19:1). The unified fractions are concentrated by evaporation and the residue is triturated with petroleum ether/ether=1:1 and suction filtered.

Workup

  1. temperaturecooling with ice
  2. stirringthe mixture is stirred for a further hour
  3. additionThen the solution is poured onto ice water
  4. extractionThe aqueous phase is extracted 3 times with 100 ml of ethyl acetate
  5. washthe combined organic phases are then washed with saline solution
  6. dry with materialdried over sodium sulphate
  7. concentrationconcentrated by evaporation
  8. custompurified over a silica gel column (particle size 0.063-0.2 mm)
  9. temperatureof increasing polarity (25:1 and 19:1)
  10. concentrationThe unified fractions are concentrated by evaporation
  11. customthe residue is triturated with petroleum ether/ether=1:1 and suction
  12. filtrationfiltered

Sources & evidence

ORD record
ord-a6547264235343ccac328d96681e3ffd
Source dataset
uspto-grants-1996_05
Patent number
US05519138

Reaction notes

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