1,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochloride → 8-(6,7-Dimethoxy-1-piperidin-1-yl-isoquinolin-4-ylmethyl)-3-isobutyl-1-methyl-3,7-dihydro-purine-2,6-dione

HRID 896062Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 896062
Cl.CN(C)[CH2:4][CH2:5][CH2:6][N:7]=[C:8]=NCC.[NH2:13][C:14]1[C:15](=[O:27])[N:16]([CH3:26])[C:17](=[O:25])[N:18]([CH2:21][CH:22]([CH3:24])[CH3:23])[C:19]=1[NH2:20].Cl[C:29]1[C:38]2[C:33](=[CH:34][C:35]([O:41][CH3:42])=[C:36]([O:39][CH3:40])[CH:37]=2)[C:32]([CH2:43][C:44](O)=O)=[CH:31][N:30]=1.[OH-].[Na+].[CH3:49]O>CO.O>[CH3:42][O:41][C:35]1[CH:34]=[C:33]2[C:38](=[CH:37][C:36]=1[O:39][CH3:40])[C:29]([N:7]1[CH2:6][CH2:5][CH2:4][CH2:49][CH2:8]1)=[N:30][CH:31]=[C:32]2[CH2:43][C:44]1[NH:13][C:14]2[C:15](=[O:27])[N:16]([CH3:26])[C:17](=[O:25])[N:18]([CH2:21][CH:22]([CH3:23])[CH3:24])[C:19]=2[N:20]=1

Komponenten

7

Edukt 4

HCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 41103394,5-Diamino-3-isobutyl-1-methylpyrimidine-2,6-dioneHCID 22226493(1-Chloro-6,7-dimethoxy-isoquinolin-4-yl)-acetic acidHCID 23721981Sodium hydroxide methanol

Produkt 1

HCID 692005398-(6,7-Dimethoxy-1-piperidin-1-yl-isoquinolin-4-ylmethyl)-3-isobutyl-1-methyl-3,7-dihydro-purine-2,6-dione

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 887MethanolLösungsmittelHCID 962WaterLösungsmittel

Versuchsvorschrift

1-(3-Dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (0.29 g, 1.9 mmol) is added to 5,6-diamino-1-isobutyl-3-methyl-1H-pyrimidine-2,4-dione (0.40 g, 1.9 mmol)) and (1-chloro-6,7-dimethoxy-isoquinolin-4-yl)-acetic acid (0.39 g, 1.78 mmol) in methanol and water and the mixture is stirred at ambient temperature for 2 hours. The methanol is evaporated and the resultant solid collected by filtration and recrystalised from ethylacetate/methanol. The resulting solid is heated under reflux with piperidine for 8 h. The solution is filtered and the resulting solution washed with water and brine, dried over sodium sulphate, filtered and concentrated. Further purification by flash silica column chromatography (eluant: ethylacetate/methanol) yields a solid which is dissolved 20% 1N NaOH/methanol and heated to reflux for 2 h. Concentration, addition of water and extraction with ethyl acetate gives an organic fraction which is washed with water and brine, dried over Na2SO4, filtered and concentrated to give 8-(6,7-dimethoxy-1-piperidin-1-yl-isoquinolin-4-ylmethyl)-3-isobutyl-1-methyl-3,7-dihydro-purine-2,6-dione, MH+ 507.

Aufarbeitung

  1. customThe methanol is evaporated
  2. filtrationthe resultant solid collected by filtration
  3. customrecrystalised from ethylacetate/methanol
  4. temperatureThe resulting solid is heated
  5. temperatureunder reflux with piperidine for 8 h
  6. filtrationThe solution is filtered
  7. washthe resulting solution washed with water and brine
  8. dry with materialdried over sodium sulphate
  9. filtrationfiltered
  10. concentrationconcentrated
  11. customFurther purification by flash silica column chromatography (eluant: ethylacetate/methanol)
  12. customyields a solid which
  13. temperatureheated
  14. temperatureto reflux for 2 h
  15. concentrationConcentration, addition of water and extraction with ethyl acetate
  16. customgives an organic fraction which
  17. washis washed with water and brine
  18. dry with materialdried over Na2SO4
  19. filtrationfiltered
  20. concentrationconcentrated

Quellen und Nachweise

ORD-Eintrag
ord-481b147af3b6440aa4cb9c6a9636a8cd
Quelldatensatz
uspto-grants-2005_07
Patentnummer
US06919337B2

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