Cyclohexene → N2-isobutyryl-O6-diphenylcarbamoyl-3'-O-azidomethyl-2'-deoxyguanosine

HRID 58513

Reaktionsgleichung

Reaktionsgleichung von HRID 58513
[C:1]([NH:6][C:7]1[N:8]=[C:9]([O:34][C:35](=[O:49])[N:36]([C:43]2[CH:48]=[CH:47][CH:46]=[CH:45][CH:44]=2)[C:37]2[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=2)[C:10]2[N:11]=[CH:12][N:13]([C:32]=2[N:33]=1)[C@@H:14]1[O:31][C@H:21]([CH2:22][O:23][Si](C(C)(C)C)(C)C)[C@@H:16]([O:17][CH2:18]SC)[CH2:15]1)(=[O:5])[CH:2]([CH3:4])[CH3:3].C1CCCCC=1.[N-:56]=[N+:57]=[N-:58].[Na+].[NH4+].[F-]>C(Cl)Cl>[C:1]([NH:6][C:7]1[N:8]=[C:9]([O:34][C:35](=[O:49])[N:36]([C:37]2[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=2)[C:43]2[CH:44]=[CH:45][CH:46]=[CH:47][CH:48]=2)[C:10]2[N:11]=[CH:12][N:13]([C:32]=2[N:33]=1)[C@@H:14]1[O:31][C@H:21]([CH2:22][OH:23])[C@@H:16]([O:17][CH2:18][N:56]=[N+:57]=[N-:58])[CH2:15]1)(=[O:5])[CH:2]([CH3:4])[CH3:3]

Komponenten

6

Edukt 4

HCID 8079CyclohexeneHCID 25516Ammonium fluorideHCID 33557Sodium AzideHCID 86638828N2-isobutyryl-O6-diphenylcarbamoyl-3'-O-(methylthiomethyl)-5'-O-(tert-butyldimethylsilyl)-2'-deoxyguanosine

Produkt 1

HCID 86638829N2-isobutyryl-O6-diphenylcarbamoyl-3'-O-azidomethyl-2'-deoxyguanosineAusbeute 36 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6344DichloromethaneLösungsmittel

Versuchsvorschrift

To 786 mg 12 (1.1 mmol) dissolved in 8 mL dry CH2Cl2 was treated with 0.56 mL cyclohexene and 180 μL SO2Cl2 (2.2 mmol) at 0° C. and stirred for 1.5 h at the same temperature. The solvent was then removed by rotary evaporation, and further dried under high vacuum for 10 minutes. The crude product was then dissolved in 5 mL dry DMF and reacted with 600 mg NaN3 (10 mmol) at 0° C. and stirred at room temperature for 3 h. Reaction mixture was then partitioned H2O/CH2Cl2, the combined organic extract was then dried over Na2SO4, and concentrated by rotary evaporation. The crude was then dissolved in 5 mL dry MeOH, treated with 500 mg NH4F (13.5 mmol) at room temperature for more than 24 h. Then MeOH solvent was removed by rotary evaporation, and partitioned (H2O/CH2Cl2). The combined organic part was dried over Na2SO4 and concentrated by rotary evaporation and purified by silica gel column chromatography resulting pure product of 14 as white powder (230 mg, ˜36% yield in three steps; hex: EtOAc 1:1 to 1:5, (Rf=˜0.3, Hex:EtOAc/1:4). HR-MS: Obs. m/z 588.2343, calcd for C28H30O6N9 588.2319 [M+H]+. 1H-NMR (DFM-d6): δH 8.64 (brs, 1H), 7.48-7.34 (m, 10H), 6.36 (t, J=7.0 Hz), 4.93 (m, 2H), 4.76 (m, 1H), 4.04 (m, 1H), 3.57 (m, 1H), 3.34 (m, 2H), 2.97 (m, 1H), 2.81 (m, 1H), and 1.10 (m, 6H).

Aufarbeitung

  1. customThe solvent was then removed by rotary evaporation
  2. customfurther dried under high vacuum for 10 minutes
  3. dissolutionThe crude product was then dissolved in 5 mL dry DMF
  4. stirringstirred at room temperature for 3 h
  5. customReaction mixture
  6. extractionpartitioned H2O/CH2Cl2, the combined organic extract
  7. dry with materialwas then dried over Na2SO4
  8. concentrationconcentrated by rotary evaporation
  9. dissolutionThe crude was then dissolved in 5 mL dry MeOH
  10. customThen MeOH solvent was removed by rotary evaporation
  11. custompartitioned (H2O/CH2Cl2)
  12. dry with materialThe combined organic part was dried over Na2SO4
  13. concentrationconcentrated by rotary evaporation
  14. custompurified by silica gel column chromatography

Quellen und Nachweise

ORD-Eintrag
ord-c719e3e560444f3e84e4aef93f2e3729
Quelldatensatz
uspto-grants-2016_09
Patentnummer
US09434989B2

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