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

HRID 1097679

반응식

HRID 1097679 반응식
[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][CH3:18])[C:4]=2[N:3]=1.[C:19]1([CH2:25][C:26]2[O:30][N:29]=[C:28]([CH2:31][CH2:32][CH2:33]O)[N:27]=2)[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=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]([CH2:33][CH2:32][CH2:31][C:28]3[N:27]=[C:26]([CH2:25][C:19]4[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=4)[O:30][N:29]=3)[C:6](=[O:15])[N:5]([CH2:16][CH2:17][CH3:18])[C:4]=2[N:3]=1

참가 물질

8

반응물 5

HCID 8083MorpholineHCID 11776TriphenylphosphineHCID 5387121Dibenzyl azodicarboxylateHCID 592995678-chloro-7-(2-propen-1-yl)-3-propyl-3,7-dihydro-1H-purine-2,6-dioneHCID 593958023-[5-(Phenylmethyl)-1,2,4-oxadiazol-3-yl]-1-propanol

생성물 1

HCID 593956928-Chloro-1-{3-[5-(phenylmethyl)-1,2,4-oxadiazol-3-yl]propyl}-3-propyl-3,7-dihydro-1H-purine-2,6-dione수율 11.3%

시약·촉매·용매 2

HCID 178418397HCID 178418397, 화합물촉매HCID 8028Tetrahydrofuran용매

실험 절차

A solution of 8-chloro-7-(2-propen-1-yl)-3-propyl-3,7-dihydro-1H-purine-2,6-dione (200 mg, 0.74 mmol) in THF (4 ml) was treated with 3-[5-(phenylmethyl)-1,2,4-oxadiazol-3-yl]-1-propanol (195 mg, 0.89 mmol) and PPh3 (254 mg, 0.96 mmol). DBAD (223 mg, 0.96 mmol) was added in one portion and the mixture was left to stir at rt under nitrogen for 18 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 product was purified on a silica SPE column using a 0-70% cyclohexane/EtOAc gradient. The product fractions were combined, concentrated by high vacuum and purified on a silica SPE column using a 0-60% cyclohexane/EtOAc gradient. The product fractions were combined and concentrated then dissolved in anhydrous THF (4 ml). The solution was degassed by high vacuum then Pd(PPh3)4 (61 mg, 0.053 mmol) and morpholine (460 μl, 5.3 mmol) were added and the mixture left to stir at rt under nitrogen for 1 day. 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 product was purified by an aminopropyl SPE using MeOH to load the compound onto the column and wash through the impurities then a 2-4% AcOH/MeOH gradient to elute the product. The product fractions were combined and concentrated to leave the title compound as a white solid (36 mg, 11%).

후처리

  1. waitthe mixture was left
  2. customThe mixture was partitioned between EtOAc and 2M HCl (aq)
  3. customThe organic layer was separated
  4. washwashed with brine
  5. dry with materialdried (MgSO4)
  6. concentrationconcentrated by high vacuum
  7. customThe crude product was purified on a silica SPE column
  8. concentrationconcentrated by high vacuum
  9. custompurified on a silica SPE column
  10. concentrationconcentrated
  11. dissolutionthen dissolved in anhydrous THF (4 ml)
  12. customThe solution was degassed by high vacuum
  13. waitthe mixture left
  14. stirringto stir at rt under nitrogen for 1 day
  15. customThe mixture was partitioned between EtOAc and 2M HCl (aq)
  16. customThe organic layer was separated
  17. washwashed with brine
  18. dry with materialdried (MgSO4)
  19. concentrationconcentrated by high vacuum
  20. customThe crude product was purified by an aminopropyl SPE
  21. washwash through the impurities
  22. washa 2-4% AcOH/MeOH gradient to elute the product
  23. concentrationconcentrated

출처 및 근거

ORD 기록
ord-9197bbb349704dbd9abcffc5d4c0ef97
출처 데이터셋
uspto-grants-2012_03
특허 번호
US08143264B2

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