Hydrochloric Acid → 6-(2,6-dichlorobenzyl)-9-hydroxy-2-isopropyl-3,4-dihydro-2H-pyrazino[1,2-c]pyrimidine-1,8-dione

HRID 2169205Notes

Reaction equation

HRID 2169205 reaction equation
C([O:8][C:9]1[C:14](=[O:15])[N:13]=[C:12]([CH2:16][C:17]2[C:22]([Cl:23])=[CH:21][CH:20]=[CH:19][C:18]=2[Cl:24])[N:11]2[CH2:25][CH2:26][N:27]([CH:30]([CH3:32])[CH3:31])[C:28](=[O:29])[C:10]=12)C1C=CC=CC=1.Cl>CO>[Cl:23][C:22]1[CH:21]=[CH:20][CH:19]=[C:18]([Cl:24])[C:17]=1[CH2:16][C:12]1[N:11]2[CH2:25][CH2:26][N:27]([CH:30]([CH3:32])[CH3:31])[C:28](=[O:29])[C:10]2=[C:9]([OH:8])[C:14](=[O:15])[N:13]=1

Participants

4

Reactant 2

HCID 313Hydrochloric AcidHCID 867258549-benzyloxy-6-(2,6-dichlorobenzyl)-2-isopropyl-3,4-dihydro-2H-pyrazino[1,2-c]pyrimidine-1,8-dione

Product 1

HCID 867258556-(2,6-dichlorobenzyl)-9-hydroxy-2-isopropyl-3,4-dihydro-2H-pyrazino[1,2-c]pyrimidine-1,8-dioneYield 30.9%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

9-Benzyloxy-6-(2,6-dichlorobenzyl)-2-isopropyl-3,4-dihydro-2H-pyrazino[1,2-c]pyrimidine-1,8-dione (65) (0.04 g, 84.7 μmol, Eq: 1.00) was suspended in methanol (0.5 ml) and HCl conc (600 mg, 0.5 ml, 16.5 mmol, Eq: 194) was added. The resulting mixture was stirred at room temperature overnight. The organic solvent was mostly removed. Aqueous NaHCO3 was added slowly. The water was removed under reduced pressure. The residue was taken up in ethanol and stirred at room temperature overnight. The suspension was filtered and the filtrate was concentrated to dryness. The remaining solid was purified by reverse phase flash chromatography (13 g C18, water/acetonitrile 0-100% acetonitrile). Product containing fractions were combined and lyophilized to of ford 6-(2,6-dichlorobenzyl)-9-hydroxy-2-isopropyl-3,4-dihydro-2H-pyrazino[1,2-c]pyrimidine-1,8-dione (66) (0.01 g, 30.6% yield) as a white solid.

Workup

  1. customThe organic solvent was mostly removed
  2. additionAqueous NaHCO3 was added slowly
  3. customThe water was removed under reduced pressure
  4. stirringstirred at room temperature overnight
  5. filtrationThe suspension was filtered
  6. concentrationthe filtrate was concentrated to dryness
  7. customThe remaining solid was purified by reverse phase flash chromatography (13 g C18, water/acetonitrile 0-100% acetonitrile)
  8. additionProduct containing fractions

Sources & evidence

ORD record
ord-4412a5e6c68a436e80d570c5b7f1dde2
Source dataset
uspto-grants-2015_06
Patent number
US09045486B2

Reaction notes

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