Diisopropylethylamine → 8-(6-Ethynyl-isoquinolin-4-ylmethyl)-3-isobutyl-1-methyl-3,7-dihydro-purine-2,6-dione

HRID 1745816Notes

Reaction equation

HRID 1745816 reaction equation
[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].CCN(C(C)C)C(C)C.[NH2:26][C:27]1[C:28](=[O:40])[N:29]([CH3:39])[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[NH:26][C:27]2[C:28](=[O:40])[N:29]([CH3:39])[C:30](=[O:38])[N:31]([CH2:34][CH:35]([CH3:37])[CH3:36])[C:32]=2[N:33]=1)#[CH:2]

Participants

5

Reactant 3

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

Product 1

HCID 222264848-(6-Ethynyl-isoquinolin-4-ylmethyl)-3-isobutyl-1-methyl-3,7-dihydro-purine-2,6-dione

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

(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 hexafluorophosphate (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 stirrred 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-1-methyl-3,7-dihydro-purine-2,6-dione, [MH]+ 388.

Workup

  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. waitstirrred 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)

Sources & evidence

ORD record
ord-af3cf75f31324196a69fb524df0c8e28
Source dataset
uspto-grants-2006_03
Patent number
US07019136B2

Reaction notes

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