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

HRID 1057097Notes

Reaction equation

HRID 1057097 reaction equation
[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]

Participants

6

Reactant 4

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

Product 1

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

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

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).

Workup

  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

Sources & evidence

ORD record
ord-2ac992b0180b4b7b9b713b4926caa2cf
Source dataset
uspto-grants-2016_07
Patent number
US09399799B2

Reaction notes

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