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

HRID 1097676

Reaktionsgleichung

Reaktionsgleichung von HRID 1097676
[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][CH2:17][CH2:18][CH2:19][CH3:20])[C:4]=2[N:3]=1.[C:21]1([CH2:27][C:28]2[O:32][N:31]=[C:30]([CH2:33][CH2:34][CH2:35]O)[N:29]=2)[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1.C1C=CC(COC(/N=N/C(OCC2C=CC=CC=2)=O)=O)=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=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]([CH2:35][CH2:34][CH2:33][C:30]3[N:29]=[C:28]([CH2:27][C:21]4[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=4)[O:32][N:31]=3)[C:6](=[O:15])[N:5]([CH2:16][CH2:17][CH2:18][CH2:19][CH3:20])[C:4]=2[N:3]=1

Komponenten

8

Edukt 5

HCID 8083MorpholineHCID 11776TriphenylphosphineHCID 5387121Dibenzyl azodicarboxylateHCID 592995577-Allyl-8-chloro-3-pentyl-1H-purine-2,6(3H,7H)-dioneHCID 593958023-[5-(Phenylmethyl)-1,2,4-oxadiazol-3-yl]-1-propanol

Produkt 1

HCID 593955278-Chloro-3-pentyl-1-{3-[5-(phenylmethyl)-1,2,4-oxadiazol-3-yl]propyl}-3,7-dihydro-1H-purine-2,6-dioneAusbeute 20 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 178418397HCID 178418397, VerbindungKatalysator2×HCID 8028TetrahydrofuranLösungsmittel

Versuchsvorschrift

To a stirred solution of 8-chloro-3-pentyl-7-(2-propen-1-yl)-3,7-dihydro-1H-purine-2,6-dione (0.20, 0.67 mmol) in THF (5 ml) was added 3-[5-(phenylmethyl)-1,2,4-oxadiazol-3-yl]-1-propanol (0.162 g, 0.74 mmol), DBAD (0.186 g, 0.81 mmol) and triphenylphosphine (0.212 g, 0.81 mmol) and the solution stirred for 18 h. To the solution was added Pd(PPh3)4 (75 mg, 0.067 mmol) and morpholine (604 μl, 6.7 mmol) were added and stirred for at rt under nitrogen for a further 3 h. 75 mg of Pd(PPh3)4 was added and the mixture left to stir for another 3 h. The mixture was partitioned between EtOAc and 2M HCl (aq). The organic layer was separated, washed with brine, dried (MgSO4) and concentrated. 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 2-4% AcOH/MeOH to elute the compound. The product fractions were combined and concentrated then further purified by MDAP. The product fractions were combined and concentrated give the title compound as a white solid (51 mg, 20%).

Aufarbeitung

  1. additionwere added
  2. stirringstirred for at rt under nitrogen for a further 3 h
  3. waitthe mixture left
  4. stirringto stir for another 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
  10. customThe crude material was purified by an aminopropyl SPE
  11. washwash through the impurities
  12. washwith 2-4% AcOH/MeOH to elute the compound
  13. concentrationconcentrated
  14. customthen further purified by MDAP
  15. concentrationconcentrated

Quellen und Nachweise

ORD-Eintrag
ord-51fe2b08ba1a4a6fa16b6c7ca620c5e2
Quelldatensatz
uspto-grants-2012_03
Patentnummer
US08143264B2

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