Trimethylsilyl triflate → 5-amino-3-[(2R,3R,5S)-5-[[tert-butyl(diphenyl)silyl]oxymethyl]-3-(1-fluoro-1-methyl-ethyl)tetrahydrofuran-2-yl]-6H-thiazolo[4,5-d]pyrimidine-2,7-dione

HRID 60768Notes

Reaction equation

HRID 60768 reaction equation
[NH2:1][C:2]1[NH:3][C:4](=[O:12])[C:5]2[S:10][C:9](=[O:11])[NH:8][C:6]=2[N:7]=1.C[Si](C([Si](C)(C)C)C(N)=O)(C)C.[Si:25]([O:42][CH2:43][C@H:44]1[O:48][CH:47](CC([O-])=O)[C@H:46]([C:53]([F:56])([CH3:55])[CH3:54])[CH2:45]1)([C:38]([CH3:41])([CH3:40])[CH3:39])([C:32]1[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=1)[C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1.C[Si](OS(C(F)(F)F)(=O)=O)(C)C>>[NH2:1][C:2]1[NH:3][C:4](=[O:12])[C:5]2[S:10][C:9](=[O:11])[N:8]([C@H:47]3[C@H:46]([C:53]([F:56])([CH3:55])[CH3:54])[CH2:45][C@@H:44]([CH2:43][O:42][Si:25]([C:38]([CH3:41])([CH3:40])[CH3:39])([C:32]4[CH:33]=[CH:34][CH:35]=[CH:36][CH:37]=4)[C:26]4[CH:27]=[CH:28][CH:29]=[CH:30][CH:31]=4)[O:48]3)[C:6]=2[N:7]=1

Participants

5

Reactant 4

HCID 65367Trimethylsilyl triflateHCID 11708267BistrimethylsilylacetamidHCID 131737115[(3R,5S)-5-[[tert-butyl(diphenyl)silyl]oxymethyl]-3-(1-fluoro-1-methyl-ethyl)tetrahydrofuran-2-yl]acetate2×HCID 1357436395-Aminothiazolo[4,5-d]pyrimidine-2,7(3H,6H)-dione

Product 1

HCID 1371902235-amino-3-[(2R,3R,5S)-5-[[tert-butyl(diphenyl)silyl]oxymethyl]-3-(1-fluoro-1-methyl-ethyl)tetrahydrofuran-2-yl]-6H-thiazolo[4,5-d]pyrimidine-2,7-dioneYield 44.4%

Conditions

Temperature
75 °C

Procedure

A mixture of 5-amino-3,6-dihydrothiazolo[4,5-d]pyrimidine-2,7-dione (162 mg, 0.87 mmol) and bis(trimethylsilyl)acetamide (527 mg, 2.61 mmol) was heated with stirring at 75° C. under argon until the mixture became clear. The mixture was cooled to room temperature. To the previous reaction mixture, [(3R,5S)-5-[[tert-butyl(diphenyl)silyl]oxymethyl]-3-(1-fluoro-1-methyl-ethyl)tetrahydrofuran-2-yl]acetate (compound 40g, 280 mg, 1.02 mmol) and trimethylsilyltrifluoromethanesulfonate (290 mg, 1.31 mmol) were introduced. The resulting mixture was heated at 75° C. under argon for 3 hours. Then the resulting mixture was concentrated in vacuo to remove the solvent and the residue was purified by column chromatography on silica gel (eluting with 0-5% methanol in DCM) to afford 225 mg of 5-amino-3-[(2R,3R,5S)-5-[[tert-butyl(diphenyl)silyl]oxymethyl]-3-(1-fluoro-1-methyl-ethyl)tetrahydrofuran-2-yl]-6H-thiazolo[4,5-d]pyrimidine-2,7-dione (compound 40h) as a brown solid. MS obsd. (ESI+) [(M+H)+]: 583.

Workup

  1. temperaturewas heated
  2. temperatureThe mixture was cooled to room temperature
  3. temperatureThe resulting mixture was heated at 75° C. under argon for 3 hours
  4. concentrationThen the resulting mixture was concentrated in vacuo
  5. customto remove the solvent
  6. customthe residue was purified by column chromatography on silica gel (eluting with 0-5% methanol in DCM)

Sources & evidence

ORD record
ord-0e9dd01146664219b6b6db1fc0bd66e0
Source dataset
uspto-grants-2016_09
Patent number
US09441008B2

Reaction notes

Loading…