Morpholine → 8-Chloro-3-ethyl-1-{3-[3-(phenylmethyl)-1,2,4-oxadiazol-5-yl]propyl}-3,7-dihydro-1H-purine-2,6-dione

HRID 1097663Notes

Reaction equation

HRID 1097663 reaction equation
[Cl:1][C:2]1[N:10](CC=C)[C:9]2[C:8](=[O:14])[NH:7][C:6](=[O:15])[N:5]([CH2:16][CH3:17])[C:4]=2[N:3]=1.[C:18]1([CH2:24][C:25]2[N:29]=[C:28]([CH2:30][CH2:31][CH2:32]O)[O:27][N:26]=2)[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1C=CC(COC(/N=N/C(OCC2C=CC=CC=2)=O)=O)=CC=1.N1CCOCC1>C1COCC1.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[Cl:1][C:2]1[NH:10][C:9]2[C:8](=[O:14])[N:7]([CH2:32][CH2:31][CH2:30][C:28]3[O:27][N:26]=[C:25]([CH2:24][C:18]4[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=4)[N:29]=3)[C:6](=[O:15])[N:5]([CH2:16][CH3:17])[C:4]=2[N:3]=1

Participants

8

Reactant 5

HCID 8083MorpholineHCID 11776TriphenylphosphineHCID 5387121Dibenzyl azodicarboxylateHCID 593955733-[3-(Phenylmethyl)-1,2,4-oxadiazol-5-yl]-1-propanolHCID 593956393-ethyl-8-chloro-7-(2-propen-1-yl)-3,7-dihydro-1H-purine-2,6-dione

Product 1

HCID 593954168-Chloro-3-ethyl-1-{3-[3-(phenylmethyl)-1,2,4-oxadiazol-5-yl]propyl}-3,7-dihydro-1H-purine-2,6-dioneYield 25%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 8028TetrahydrofuranSolvent

Procedure

A solution of 8-chloro-3-ethyl-7-(2-propen-1-yl)-3,7-dihydro-1H-purine-2,6-dione (150 mg, 0.59 mmol) in anhydrous THF (4 ml) was treated with 3-[3-(phenylmethyl)-1,2,4-oxadiazol-5-yl]-1-propanol (154 mg, 0.71 mmol) and triphenylphosphine (200 mg, 0.76 mmol). DBAD (162 mg, 0.71 mmol) was added in one portion and the mixture was left to stir at rt, under nitrogen for 18 h. The mixture was degassed by high vacuum then Pd(PPh3)4 (68 mg, 0.059 mmol) and morpholine (515 μl, 5.9 mmol) were added. The mixture was left to stir at rt, under nitrogen, for 3 h. The mixture was partitioned between EtOAc and 2M HCl (aq). The organic layer was separated, washed with brine, dried (MgSO4) and concentrated by high vacuum. The crude material was purified by an aminopropyl SPE using MeOH to load the compound onto the column and wash through the impurities, then with 2% AcOH/MeOH to elute the compound. The UV active fractions were combined and concentrated by high vacuum. The product was further purified by MDAP. The product fractions were combined and concentrated to give the title compound as a white solid (61 mg, 25%).

Workup

  1. waitthe mixture was left
  2. customThe mixture was degassed by high vacuum
  3. waitThe mixture was left
  4. stirringto stir at rt, under nitrogen, for 3 h
  5. customThe mixture was partitioned between EtOAc and 2M HCl (aq)
  6. customThe organic layer was separated
  7. washwashed with brine
  8. dry with materialdried (MgSO4)
  9. concentrationconcentrated by high vacuum
  10. customThe crude material was purified by an aminopropyl SPE
  11. washwash through the impurities
  12. washwith 2% AcOH/MeOH to elute the compound
  13. concentrationconcentrated by high vacuum
  14. customThe product was further purified by MDAP
  15. concentrationconcentrated

Sources & evidence

ORD record
ord-65f19b7c373646efa8fa9e877969f502
Source dataset
uspto-grants-2012_03
Patent number
US08143264B2

Reaction notes

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