Hydrochloric Acid → 4-(2,6-dioxo-1,3-dipropyl-2,3,6,7-tetrahydro-1H-purin-8-yl)-bicyclo[2.2.2]octane-1-carbaldehyde

HRID 2105689Notes

Reaction equation

HRID 2105689 reaction equation
[OH:1][CH2:2][C:3]12[CH2:10][CH2:9][C:6]([C:11]3[NH:19][C:18]4[C:17](=[O:20])[N:16]([CH2:21][CH2:22][CH3:23])[C:15](=[O:24])[N:14]([CH2:25][CH2:26][CH3:27])[C:13]=4[N:12]=3)([CH2:7][CH2:8]1)[CH2:5][CH2:4]2.C(N(CC)CC)C.C(OCC)(=O)C.Cl>CS(C)=O>[O:24]=[C:15]1[N:14]([CH2:25][CH2:26][CH3:27])[C:13]2[N:12]=[C:11]([C:6]34[CH2:7][CH2:8][C:3]([CH:2]=[O:1])([CH2:10][CH2:9]3)[CH2:4][CH2:5]4)[NH:19][C:18]=2[C:17](=[O:20])[N:16]1[CH2:21][CH2:22][CH3:23]

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 8471TriethylamineHCID 8857Ethyl AcetateHCID 119956518-(4-Hydroxymethyl-bicyclo[2.2.2]oct-1-yl)-1,3-dipropyl-3,7-dihydro-purine-2,6-dione

Product 1

HCID 99294054-(2,6-dioxo-1,3-dipropyl-2,3,6,7-tetrahydro-1H-purin-8-yl)-bicyclo[2.2.2]octane-1-carbaldehyde

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent

Procedure

8-(4-Hydroxymethylbicyclo[2.2.2]oct-1-yl)-1,3-dipropyl-3,7-dihydropurine-2,6-dione (X, Example 86a, 1 wt) and dimethyl sulphoxide-(4 vol)are mixed and stirred under nitrogen; the mixture is stirred for 5 to 15 mins and triethylamine (2.42 vol) is added. A mixture of sulphur trioxide pyridine complex (1.275 wt) in dimethyl sulphoxide (6 vol) is added, maintaining the internal temperature below 30°. The temperature is adjusted to 14 to 20°and the reaction mixture is then stirred at 14 to 20° for 16 to 20 hours until complete by NMR. If there is any starting alcohol remaining sulphur trioxide pyridine complex (0.15 wt) is added and the reaction stirred for a further 2 to 3 hours at 14 to 20°. Ethyl acetate (20 vol) and hydrochloric acid (1 M, 10 vol) are added to the reaction mixture and stirred vigorously for 5 to 15 mins. The phases are separated and the organic phase is washed with hydrochloric acid (1 M, 10 vol). The phases are separated and the organic phase is again washed with hydrochloric acid (1 M, 10 vol). The phases are separated and the organic phase is washed with saline (5 vol); dried over magnesium sulphate (0.5 wt) for 5 to 10 mins and filtered. The filter cake is washed with ethyl acetate (1 vol). The solvent is removed under reduced pressure at 40 to 45° to give the title compound.

Workup

  1. stirringthe mixture is stirred for 5 to 15 mins
  2. additionis added
  3. temperaturemaintaining the internal temperature below 30°
  4. stirringis then stirred at 14 to 20° for 16 to 20 hours until complete by NMR
  5. additionis added
  6. stirringthe reaction stirred for a further 2 to 3 hours at 14 to 20°
  7. stirringstirred vigorously for 5 to 15 mins
  8. customThe phases are separated
  9. washthe organic phase is washed with hydrochloric acid (1 M, 10 vol)
  10. customThe phases are separated
  11. washthe organic phase is again washed with hydrochloric acid (1 M, 10 vol)
  12. customThe phases are separated
  13. washthe organic phase is washed with saline (5 vol)
  14. dry with materialdried over magnesium sulphate (0.5 wt) for 5 to 10 mins
  15. filtrationfiltered
  16. washThe filter cake is washed with ethyl acetate (1 vol)
  17. customThe solvent is removed under reduced pressure at 40 to 45°

Sources & evidence

ORD record
ord-024fc4214be642588bb3c4f5e5cf7498
Source dataset
uspto-grants-2009_08
Patent number
US07579354B2

Reaction notes

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