Diisopropylethylamine → 8-(6-Ethynyl-isoquinolin-4-ylmethyl)-3-isobutyl-methyl-3,7dihydro-purine-2,6-dione

HRID 900716Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 900716
[C:1]([C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][CH:12]=1)[CH:9]=[N:8][CH:7]=[C:6]2[CH2:13][C:14](O)=O)#[CH:2].[CH3:17]CN(C(C)C)C(C)C.[NH2:26][C:27]1[C:28](=[O:40])[N:29](C)[C:30](=[O:38])[N:31]([CH2:34][CH:35]([CH3:37])[CH3:36])[C:32]=1[NH2:33]>CN(C=O)C>[C:1]([C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][CH:12]=1)[CH:9]=[N:8][CH:7]=[C:6]2[CH2:13][C:14]1[N:26]([CH3:17])[C:27]2[C:28](=[O:40])[NH:29][C:30](=[O:38])[N:31]([CH2:34][CH:35]([CH3:37])[CH3:36])[C:32]=2[N:33]=1)#[CH:2]

Komponenten

5

Edukt 3

HCID 81531DiisopropylethylamineHCID 41103394,5-Diamino-3-isobutyl-1-methylpyrimidine-2,6-dioneHCID 22226561(6-Ethynyl-isoquinolin-4-yl)-acetic acid

Produkt 1

HCID 866050528-(6-Ethynyl-isoquinolin-4-ylmethyl)-3-isobutyl-methyl-3,7dihydro-purine-2,6-dione

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6228DimethylformamideLösungsmittel2×

Versuchsvorschrift

(6-Ethynyl-isoquinolin-4-yl)-acetic acid (58 mg, 0.28 mmol) is dissolved in DMF (1 ml) and O-(7-azabenzotriazo-1-yl)-N,N,N′,N′-tetramethyluronium hexafluorophosphatc (0.125 g, 0.33 mmol) and Hunig's base (0.180 ml, 1.03 mmol) are added, followed by a solution of 5,6-diamino-1-isobutyl-3-methyl-1H-pyrimidine-2,4-dione (58 mg, 0.28 mmol) in DMF (0.7 ml). The reaction is stirred at room temperature for 2 hours. The solvent is evaporated and the residue purified by flash column chromatography (30:1 dichloromethane-methanol elution). The intermediate is dissolved in methanol (2 ml) and water (2.75 ml) added, followed by 4M aqueous sodium hydroxide (0.25 ml). The reaction is heated at 40° C. for 2 hours, then stirred for 16 hours at ambient temperature. The solvent is evaporated and the crude product purified by flash column chromatography (30:1 dichloromethane-methanol elution) to afford 8-(6-ethynyl-isoquinolin-4-ylmethyl)-3-isobutyl-methyl-3,7dihydro-purine-2,6-dione, [MH]+ 388.

Aufarbeitung

  1. customThe solvent is evaporated
  2. customthe residue purified by flash column chromatography (30:1 dichloromethane-methanol elution)
  3. dissolutionThe intermediate is dissolved in methanol (2 ml)
  4. additionwater (2.75 ml) added
  5. temperatureThe reaction is heated at 40° C. for 2 hours
  6. stirringstirred for 16 hours at ambient temperature
  7. customThe solvent is evaporated
  8. customthe crude product purified by flash column chromatography (30:1 dichloromethane-methanol elution)

Quellen und Nachweise

ORD-Eintrag
ord-a24363affbb04b49bc416c8f5edcf829
Quelldatensatz
uspto-grants-2008_04
Patentnummer
US07361661B2

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