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

HRID 1745824Notes

Reaction equation

HRID 1745824 reaction equation
Cl.[CH3:2][N:3](C)[CH2:4]CCN=C=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>CO.O>[CH3:2][N:3]([CH3:4])[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]2[NH:13][C:14]3[C:15](=[O:27])[N:16]([CH3:26])[C:17](=[O:25])[N:18]([CH2:21][CH:22]([CH3:23])[CH3:24])[C:19]=3[N:20]=2)=[CH:31][N:30]=1

Participants

6

Reactant 3

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 acid

Product 1

HCID 691977408-(1-Dimethylamino-6,7-dimethoxy-isoquinolin-4-ylmethyl)-3-isobutyl-1-methyl-3,7-dihydro-purine-2,6-dione

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 962WaterSolvent

Procedure

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 in a sealed tube (100° C., 8 h) with 40% aqueous dimethylamine. The mixture is evaporated and extracted with ethylacetate. The ethylacetate solution is then washed with water and brine, dried over sodium sulphate, filtered and concentrated. Further purification by flash silica column chromatography (eluant: ethylacetate/methanol) yields 8-(1-dimethylamino-6,7-dimethoxy-isoquinolin-4-ylmethyl)-3-isobutyl-1-methyl-3,7-dihydro-purine-2,6-dione, MH+ 467.

Workup

  1. customThe methanol is evaporated
  2. filtrationthe resultant solid collected by filtration
  3. customrecrystalised from ethylacetate/methanol
  4. temperatureThe resulting solid is heated in a sealed tube (100° C., 8 h) with 40% aqueous dimethylamine
  5. customThe mixture is evaporated
  6. extractionextracted with ethylacetate
  7. washThe ethylacetate solution is then 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)

Sources & evidence

ORD record
ord-5436d41c436647bf9e7c1b51fab7cfdc
Source dataset
uspto-grants-2006_03
Patent number
US07019136B2

Reaction notes

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