Hexamethyldisilazane → 7-Amino-3-(2,3,5-tri-O-benzoyl-beta-D-ribofuranosyl)thiazolo[4,5-d]pyrimidin-2-one

HRID 1638536Notes

Reaction equation

HRID 1638536 reaction equation
[NH2:1][C:2]1[C:3]2[S:10][C:9](=[O:11])[NH:8][C:4]=2[N:5]=[CH:6][N:7]=1.C[Si](N[Si](C)(C)C)(C)C.C(O[CH:25]1[O:47][C@H:46]([CH2:48][O:49][C:50](=[O:57])[C:51]2[CH:56]=[CH:55][CH:54]=[CH:53][CH:52]=2)[C@@H:36]([O:37][C:38](=[O:45])[C:39]2[CH:44]=[CH:43][CH:42]=[CH:41][CH:40]=2)[C@H:26]1[O:27][C:28](=[O:35])[C:29]1[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=1)(=O)C.[Si](OS(C(F)(F)F)(=O)=O)(C)(C)C>CCO.C(Cl)Cl.CC(C)=O.C(Cl)Cl>[NH2:1][C:2]1[C:3]2[S:10][C:9](=[O:11])[N:8]([C@@H:25]3[O:47][C@H:46]([CH2:48][O:49][C:50](=[O:57])[C:51]4[CH:56]=[CH:55][CH:54]=[CH:53][CH:52]=4)[C@@H:36]([O:37][C:38](=[O:45])[C:39]4[CH:44]=[CH:43][CH:42]=[CH:41][CH:40]=4)[C@H:26]3[O:27][C:28](=[O:35])[C:29]3[CH:30]=[CH:31][CH:32]=[CH:33][CH:34]=3)[C:4]=2[N:5]=[CH:6][N:7]=1

Participants

8

Reactant 4

HCID 13838HexamethyldisilazaneHCID 65367Trimethylsilyl triflateHCID 109292421-O-Acetyl-2,3,5-tri-O-benzoyl-D-ribofuranoseHCID 145057617-Aminothiazolo[4,5-d]pyrimidin-2(3H)-one

Product 1

HCID 145057657-Amino-3-(2,3,5-tri-O-benzoyl-beta-D-ribofuranosyl)thiazolo[4,5-d]pyrimidin-2-one

Reagents, catalysts & solvents 3

HCID 702EthanolSolventHCID 6344DichloromethaneSolventHCID 21584124Propan-2-one--dichloromethane (1/1)Solvent

Procedure

Compound 30 (1.22 g, 7.25 mmol) was glycosylated as described for the preparation of 6, requiring HMDS (35 mL), benzoyl-blocked sugar (5: 4.4 g, 8.7 mmol) and TMS-triflate (2.0 mL, 10.3 mmol). After stirring overnight at room temperature, the reaction mixture was refluxed for 2 days and then worked up in the usual manner. The crude mixture was subjected to flash silica gel column chromatography using a gradient of methylene chloride to methylene chloride-acetone 10:1 (v/v) and yielded two products. The first to elute from the column was assumed by 1H NMR to be a bis-glycoside which amounted to 660 mg. The second and major product off the column was obtained as a foam and assigned as the desired 3-ribosyl isomer by UV and 1H NMR: yield 1.04 g (24%): UV λmax (EtOH) 232 nm (ε), 283 (): 1H NMR (DMSO-d6) δ6.34 (t, 1H, C1,H), 7.39-7.98 (m, 17H, benzoyl aromatics and NH2, 8.19 (s, 1H, C5H), and other sugar protons. Anal. Calcd. for C, 60.78: H, 3.95: N, 9.15: S, 5.23. Found: 3.93: N, 8.13: S, 4.85.

Workup

  1. customas described for the preparation of 6
  2. temperaturethe reaction mixture was refluxed for 2 days
  3. customyielded two products
  4. washThe first to elute from the column
  5. customThe second and major product off the column was obtained as a foam

Sources & evidence

ORD record
ord-8d3e9115e20c4c32a8cb1bb23f53bd3d
Source dataset
uspto-grants-1989_11
Patent number
US04880784

Reaction notes

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