Trimethylsilyl triflate → Guanine

HRID 1956820Notes

Reaction equation

HRID 1956820 reaction equation
C1(C[O:8][C:9]2[NH:17][C:16]([NH:18]C(=O)C)=[N:15][C:14]3[C:10]=2[N:11]=[CH:12][N:13]=3)C=CC=CC=1.C(O[C@@H]1O[C@H](COC(=O)C)[C@@H](OC(=O)C)[C@H](OC(=O)C)[C@H]1NC(=O)C(F)(F)F)(=O)C.[Si](OS(C(F)(F)F)(=O)=O)(C)(C)C.C([O-])(O)=O.[Na+]>CC#N>[NH:17]1[C:9](=[O:8])[C:10]2[NH:11][CH:12]=[N:13][C:14]=2[N:15]=[C:16]1[NH2:18]

Participants

6

Reactant 4

HCID 65367Trimethylsilyl triflateHCID 516892Sodium BicarbonateHCID 10623108HCID 10623108, compoundHCID 178474412HCID 178474412, compound

Product 1

HCID 135398634GuanineYield 65.6%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Conditions

Temperature
80 °C

Procedure

To 5 g (17.65 mmol) of N-[6-(phenylmethoxy)-1H-purin-2-yl]-acetamide was added 150 mL of dry CH3CN and 9.60 mL (38.34 mmol) of BSA and this mixture was stirred at 80° C. for 3 h. At this time, 15.65 g (33.80 mmol) of 2-deoxy-2-[(trifluoroacetyl)amino]-β-D-glucopyranose-1,3,4,6-tetraacetate was added followed by 6.80 mL (35.30 mmol) of TMSOTf. This mixture was heated with stirring at 80° C. for 12 hours. At this time, the reaction mixture was poured into 200 mL of saturated, aqueous NaHCO3 and this mixture was extracted twice with EtOAc. The combined organic layers were washed once with H2O and brine before drying over MgSO4. The crude product was obtained by filtration and concentration of the filtrate in vacuo to a brownish foam. The glycosylation product was obtained by silica gel column chromatography eluted with 50% to 75% EtOAc / hexanes. Appropriate fractions were collected and further purified by normal phase preparative HPLC eluting prepacked silica cartridges with 50% EtOAc/hexanes. In this manner, 1.75 g (15% yield) of the desired product, N-[6-(phenylmethoxy)-9-[3,4,6-tris-O-acetyl-2-deoxy-2-[(trifluoroacetyl)amino]-β-D-glucopyranosyl]-1H-purin-2-yl]acetamide, was isolated. 1H NMR: (CDCl3): guanine H-8 8.42 (s, 1H), anomeric H-1 6.19 (d, 1H), benzyl methylene 5.62 (m, 2H), N-acetamide methyl 2.30 (s, 3H). FAB-MS: m/z 667 for (M+1))+.

Workup

  1. temperatureThis mixture was heated
  2. stirringwith stirring at 80° C. for 12 hours
  3. extractionthis mixture was extracted twice with EtOAc
  4. washThe combined organic layers were washed once with H2O and brine
  5. dry with materialbefore drying over MgSO4
  6. customThe crude product was obtained by filtration and concentration of the filtrate in vacuo to a brownish foam
  7. customThe glycosylation product was obtained by silica gel column chromatography
  8. washeluted with 50% to 75% EtOAc / hexanes
  9. customAppropriate fractions were collected
  10. customfurther purified by normal phase preparative HPLC
  11. washeluting prepacked silica cartridges with 50% EtOAc/hexanes

Sources & evidence

ORD record
ord-c59b0e298ff141d89fec942ffa358398
Source dataset
uspto-grants-1998_07
Patent number
US05780607

Reaction notes

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