1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → 3-Isobutyl-8-(5,6-dimethoxy-isoquinolin-4-ylmethyl)-1-methyl-3,7-dihydro-purine-2,6-dione

HRID 900719Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 900719
CN(C)CCCN=C=NCC.[NH2:12][C:13]1[C:14](=[O:26])[N:15]([CH3:25])[C:16](=[O:24])[N:17]([CH2:20][CH:21]([CH3:23])[CH3:22])[C:18]=1[NH2:19].[CH3:27][O:28][C:29]1[C:38]([O:39][CH3:40])=[CH:37][CH:36]=[C:35]2[C:30]=1[C:31]([CH2:41][C:42](O)=O)=[CH:32][N:33]=[CH:34]2.ON1C2C=CC=CC=2N=N1>ClCCl.O>[CH2:20]([N:17]1[C:18]2[N:19]=[C:42]([CH2:41][C:31]3[C:30]4[C:35](=[CH:36][CH:37]=[C:38]([O:39][CH3:40])[C:29]=4[O:28][CH3:27])[CH:34]=[N:33][CH:32]=3)[NH:12][C:13]=2[C:14](=[O:26])[N:15]([CH3:25])[C:16]1=[O:24])[CH:21]([CH3:22])[CH3:23]

Komponenten

6

Edukt 4

HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 41103394,5-Diamino-3-isobutyl-1-methylpyrimidine-2,6-dioneHCID 22226531(5,6-Dimethoxy-isoquinolin-4-yl)-acetic acid

Produkt 1

HCID 222265033-Isobutyl-8-(5,6-dimethoxy-isoquinolin-4-ylmethyl)-1-methyl-3,7-dihydro-purine-2,6-dione

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 21908982Water methylene chlorideLösungsmittel

Versuchsvorschrift

1-(3-Dimethylaminopropyl)-3-ethylcarbodiimide (20.6 ml, 0.1 mol) is added to a mixture of 5,6-diamino-1-isobutyl-3-methyl-1H-pyrimidine-2,4-dione (20 g, 0.094 mol), (5,6-dimethoxy-isoquinolin-4-yl)-acetic acid (26.7 g, 0.094 mol), and 1-hydroxybenzotriazole (19.2 g, 0.142 mol) in 1:1 dichloromethane-water (400 ml). The reaction is stirred at ambient temperature for 4.5 hours and the resultant solid collected by filtration. Slurrying in water (500 ml), filtration and washing with water (250 ml) followed by drying, further trituration with methanol and drying gives an intermediate together with slightly less pure material from concentration of the methanol triturate. The intermediate (16.08 g) is dissolved in water (100 ml) and methanol (100 ml) followed by the addition of 4M aqueous sodium hydroxide (56 ml) and the resultant solution is heated at 70° C. over night. After cooling to ambient temperature, the methanol is evaporated and the residue acidified to pH 1 with concentrated hydrochloric acid. The resultant hydrochloride salt is collected by filtration and dried. The product is then be converted to the free base by treatment with aqueous sodium hydroxide to pH 11 and washing with water to afford 3-isobutyl-8-(5,6-dimethoxy-isoquinolin-4-ylmethyl)-1-methyl-3,7-dihydro-purine-2,6-dione [MH]+ 424.6.

Aufarbeitung

  1. filtrationthe resultant solid collected by filtration
  2. filtrationfiltration
  3. washwashing with water (250 ml)
  4. customby drying
  5. dry with materialfurther trituration with methanol and drying
  6. customgives an intermediate together with slightly less pure material from concentration of the methanol
  7. customtriturate
  8. dissolutionThe intermediate (16.08 g) is dissolved in water (100 ml)
  9. additionmethanol (100 ml) followed by the addition of 4M aqueous sodium hydroxide (56 ml)
  10. temperaturethe resultant solution is heated at 70° C. over night
  11. temperatureAfter cooling to ambient temperature
  12. customthe methanol is evaporated
  13. filtrationThe resultant hydrochloride salt is collected by filtration
  14. customdried
  15. washwashing with water

Quellen und Nachweise

ORD-Eintrag
ord-43631f1fab044157868b767cb7ab9693
Quelldatensatz
uspto-grants-2008_04
Patentnummer
US07361661B2

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