Potassium Hydroxide → Imatinib amine

HRID 1920037Notes

Reaction equation

HRID 1920037 reaction equation
[Na].O=[C:3]([C:7]1[CH:8]=[N:9][CH:10]=[CH:11][CH:12]=1)[CH2:4][CH:5]=O.[CH3:13][C:14]1[CH:19]=[CH:18][C:17]([NH2:20])=[CH:16][C:15]=1[NH:21][C:22]([NH2:24])=[NH:23].[OH-].[K+]>C(O)CCC.C(O)(=O)C>[CH3:13][C:14]1[CH:19]=[CH:18][C:17]([NH2:20])=[CH:16][C:15]=1[NH:21][C:22]1[N:24]=[C:3]([C:7]2[CH:8]=[N:9][CH:10]=[CH:11][CH:12]=2)[CH:4]=[CH:5][N:23]=1

Participants

7

Reactant 4

HCID 14797Potassium HydroxideHCID 5360545SodiumHCID 43114742HCID 43114742, compoundHCID 178426381HCID 178426381, compound

Product 1

HCID 9965429Imatinib amine

Reagents, catalysts & solvents 2

HCID 176Acetic AcidSolventHCID 2631-ButanolSolvent

Procedure

Under inert atmosphere, 16 g sodium salt of β-oxo-3-pyridinepropanal, with HPLC purity of 99% (A %) and 25% salt content (residue by calcination), and 11.7 g (2-methyl-5-aminophenyl)guanidine in 115 mL n-butanol is suspended. 9 mL acetic acid is added, and the mixture is stirred at room temperature for an hour. 6 g potassium hydroxide is added portionwise, and the mixture is refluxed for 18 hours, removing the water with a Dean Stark apparatus. Once completed the conversion, the suspension is cooled and the organic layer is washed with water. The organic layer is concentrated to a small volume, and toluene is added. The precipitate is filtrated, yielding, upon drying, 15.5 g of product with HPLC purity of 99.2% (A %), identified through LC-MS and 1H-NMR.

Workup

  1. temperaturethe mixture is refluxed for 18 hours
  2. customremoving the water with a Dean Stark apparatus
  3. temperaturethe suspension is cooled
  4. washthe organic layer is washed with water
  5. concentrationThe organic layer is concentrated to a small volume, and toluene
  6. additionis added
  7. filtrationThe precipitate is filtrated
  8. customyielding
  9. customupon drying

Sources & evidence

ORD record
ord-33dced4969a047a690454452938d75dd
Source dataset
uspto-grants-2012_05
Patent number
US08168787B2

Reaction notes

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