Trifluoroacetic anhydride → O6-Methyl-2'-deoxyguanosine

HRID 36000Notes

Reaction equation

HRID 36000 reaction equation
[C@@H:1]1([N:9]2[C:19]3[N:18]=[C:16]([NH2:17])[NH:15][C:13](=[O:14])[C:12]=3[N:11]=[CH:10]2)[O:8][C@H:5]([CH2:6][OH:7])[C@@H:3]([OH:4])[CH2:2]1.F[C:21](F)(F)C(OC(=O)C(F)(F)F)=O.C[O-].[Na+].Cl.N1C=CC=CC=1>N1C=CC=CC=1.CO>[NH2:17][C:16]1[N:18]=[C:19]2[C:12]([N:11]=[CH:10][N:9]2[C@@H:1]2[O:8][C@H:5]([CH2:6][OH:7])[C@@H:3]([OH:4])[CH2:2]2)=[C:13]([O:14][CH3:21])[N:15]=1

Participants

7

Reactant 4

HCID 9845Trifluoroacetic anhydrideHCID 10176127Pyridinium chlorideHCID 10942334Sodium MethoxideHCID 135398592Deoxyguanosine

Product 1

HCID 73317O6-Methyl-2'-deoxyguanosineYield 64%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 1049PyridineSolvent2×

Procedure

To 2 mmol of deoxyguanosine, dried by evaporation of pyridine and suspended in 10 mL of dry pyridine was added dropwise 2.3 mL (16 mmol) of trifluoroacetic anhydride, with cooling in an ice both. After ten minutes a suspension of 4.3 g of sodium methoxide in 300 mL of methanol was added dropwise. After a further 24 hrs, the mixture was treated with a solution of pyridine hydrochloride (12 mL of pyridine/4 mL conc HCl). The excess acid was destroyed by addition of 2 g of sodium bicarbonate and the mixture was evaporated to dryness. The residue was dissolved in water and purified on a Dynamax reversed-phase hplc column using a gradient of 2-5% acetonitrile in water in 45 min at a flow rate of 6 mL/min. Evaporation of appropriate fractions gave 0.36 g (60%) of pure 2-amino-6-methoxy-9-(2-deoxy-Beta-D-erythro-pentofuranosyl)purine. A crystalline sample was obtained by crystallization from water, mp 155°-7°. UVmax (MeOH) 281 nm; UVmin 281 nm; 1H NMR (DMSO-d6) delta (ppm) 8.07 (s, 1,H8), 6.43 (br s, 2, NH2), 6.20("t", 1, Japp =6.9 Hz, H1'), 5.27 (d, 1, J=3.8 Hz, 3'-OH), 4.98 (t, 1, J=5.5 Hz, 5'-OH) , 4.35 (m,1,H3'), 4.00 (s, 3, OCH3), 3.82 (m, 1, H4'), 3.53 (m, 2, H5',5'), 2.57 & 2.22 (m & m, 1 & 1, H2' & H2"). Anal. Calcd. for C11H15N5O4.H2O: C, 44.15; H, 5.72; N, 23.40. Found: C, 44.15; H, 5.83; N, 23.43.

Workup

  1. additionwas added dropwise
  2. customThe excess acid was destroyed by addition of 2 g of sodium bicarbonate
  3. customthe mixture was evaporated to dryness
  4. dissolutionThe residue was dissolved in water
  5. custompurified on a Dynamax reversed-phase hplc column
  6. customin 45 min
  7. customEvaporation of appropriate fractions

Sources & evidence

ORD record
ord-3735645ca06e4806b931b2c471525d9e
Source dataset
uspto-grants-1995_05
Patent number
US05412088

Reaction notes

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