Chlorotrimethylsilane → 1-(2',3',5'-Tri-o-benzoyl-beta-l-ribofuranosyl)pyridine-4-one-3-carboxamide

HRID 1368713Notes

Reaction equation

HRID 1368713 reaction equation
C[Si](C)(C)N[Si](C)(C)C.Cl[Si](C)(C)C.[N:15]1[CH:20]=[CH:19][C:18](=[O:21])[CH:17]([C:22]([NH2:24])=[O:23])[CH:16]=1.C(O[CH:29]1[O:51][C@@H:50]([CH2:52][O:53][C:54](=[O:61])[C:55]2[CH:60]=[CH:59][CH:58]=[CH:57][CH:56]=2)[C@H:40]([O:41][C:42](=[O:49])[C:43]2[CH:48]=[CH:47][CH:46]=[CH:45][CH:44]=2)[C@@H:30]1[O:31][C:32](=[O:39])[C:33]1[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=1)(=O)C.Cl[Sn](Cl)(Cl)Cl>C(Cl)Cl.C([O-])(O)=O.[Na+]>[C:32]([O:31][C@H:30]1[C@@H:40]([O:41][C:42](=[O:49])[C:43]2[CH:48]=[CH:47][CH:46]=[CH:45][CH:44]=2)[C@H:50]([CH2:52][O:53][C:54](=[O:61])[C:55]2[CH:56]=[CH:57][CH:58]=[CH:59][CH:60]=2)[O:51][C@@H:29]1[N:15]1[CH:20]=[CH:19][C:18](=[O:21])[C:17]([C:22]([NH2:24])=[O:23])=[CH:16]1)(=[O:39])[C:33]1[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=1

Participants

8

Reactant 5

HCID 6397ChlorotrimethylsilaneHCID 13838HexamethyldisilazaneHCID 24287Tin tetrachlorideHCID 126715131-o-Acetyl-2,3,5-tri-o-benzoyl-l-riboseHCID 69001467Pyridine-4-one-3-carboxamide

Product 1

HCID 120431211-(2',3',5'-Tri-o-benzoyl-beta-l-ribofuranosyl)pyridine-4-one-3-carboxamideYield 9%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 516892Sodium BicarbonateSolvent

Procedure

To a mixture of hexamethyldisilazane (50 mL, 239.77 mmol) and chlorotrimethylsilane (1.0 mL, 21.43 mmol) was added pyridine-4-one-3-carboxamide (1.38 g, 10.0 mmol) (Prepared by the procedure reported: W. C. J. Ross, J. Chem. Soc., C, 1816, (1966); W. Herz and D. R. K. Murty, J. Org. Chem., 26, 122, 1961). The mixture was refluxed with stirring for 2 h and then evaporated to dryness under vacuum and further dried under high vacuum for 2 h at 60° C. The dry gummy residue was suspended in freshly distilled 1,2-dichlorethane (50 mL) and to this suspension was added 1-O-acetyl-2,3,5-tri-O-benzoyl-L-ribofuranose(5.06 g, 10.0 mmol) and freshly distilled SnCl4 (1.0 mL, 8.52 mmol). The reaction mixture was refluxed for 1.5 h, cooled and diluted with CH2Cl2 (100 mL) and sat. aqueous NaHCO3 (25 mL). The mixture was filtered through celite and the bed was washed with CH2Cl2 (20 mL). The organic phase was separated, washed with water until the washings are neutral, dried over anhydrous sodium sulfate. The organic extract was evaporated to dryness to give a gummy residue. The residue was purified by flash chromatography over silica gel using CH2Cl2→EtOAc as the eluent. Pure fractions were pooled and concentrated to provide 0.50 g (9%) of 33 as white foam: 1H NMR (CDCl3): δ4.94 (m, 3H, C4′H and C5′H), 6.12 (m, 1H), 6.20 (m, 1H), 6.32 (d, 1H) and 7.20-8.30 (m, 20H).

Workup

  1. customPrepared by the procedure
  2. temperatureThe mixture was refluxed
  3. customevaporated to dryness under vacuum
  4. customfurther dried under high vacuum for 2 h at 60° C
  5. temperatureThe reaction mixture was refluxed for 1.5 h
  6. temperaturecooled
  7. filtrationThe mixture was filtered through celite
  8. washthe bed was washed with CH2Cl2 (20 mL)
  9. customThe organic phase was separated
  10. washwashed with water until the washings
  11. dry with materialdried over anhydrous sodium sulfate
  12. extractionThe organic extract
  13. customwas evaporated to dryness
  14. customto give a gummy residue
  15. customThe residue was purified by flash chromatography over silica gel
  16. concentrationconcentrated

Sources & evidence

ORD record
ord-e3613ea41f79410b93369fedaf31dd84
Source dataset
uspto-grants-2003_06
Patent number
US06573248B2

Reaction notes

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