Imidazole → HCID 10451163, compound

HRID 2253915Notes

Reaction equation

HRID 2253915 reaction equation
[F:1][C:2]1[C:3](=[O:17])[NH:4][C:5](=[O:16])[N:6]([CH:15]=1)[C@@H:7]1[O:14][C@H:11]([CH2:12][OH:13])[C@@H:9]([OH:10])[CH2:8]1.C1(C(Cl)(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.CN(C1C=CC=CN=1)C.N1C=CN=C1.[Si:52](Cl)([C:55]([CH3:58])([CH3:57])[CH3:56])([CH3:54])[CH3:53]>N1C=CC=CC=1>[Si:52]([O:10][C@@H:9]1[C@@H:11]([CH2:12][OH:13])[O:14][C@@H:7]([N:6]2[CH:15]=[C:2]([F:1])[C:3](=[O:17])[NH:4][C:5]2=[O:16])[CH2:8]1)([C:55]([CH3:58])([CH3:57])[CH3:56])([CH3:54])[CH3:53]

Participants

7

Reactant 5

HCID 795ImidazoleHCID 5790FloxuridineHCID 6456Trityl chlorideHCID 218852-DimethylaminopyridineHCID 28928tert-Butyldimethylsilyl chloride

Product 1

HCID 10451163HCID 10451163, compoundYield 48.4%

Reagents, catalysts & solvents 1

HCID 1049PyridineSolvent

Conditions

Temperature
80 °C

Procedure

To a solution of 5-fluoro-2'-deoxyuridine (14, 1.00 g, 4.06 mmol) in pyridine (7 ml) was added triphenylmethyl chloride (1.25 g, 4.47 mmol) and dimethylaminopyridine (0.4 g, 3.05 mmol). The mixture was allowed to stir at 80° C. for 30 min. The pyridine was removed under reduced pressure and the residue dissolved in DMF (4 ml). Imidazole (0.67 g, 9.77 mmol) and t-butyldimethylsilyl chloride (0.74 g, 4.88 mmol) were added, and the mixture was allowed to stir overnight at room temperature. The DMF was removed under pressure, and the residue was dissolved in 80% aqueous acetic acid (5 ml). The mixture was allowed to reflux for 30 min, cooled, and neutralized with NaOH. The mixture was lyophilized, and the residue was purified by chromatography (1:1 EtOAc:hexanes) to give 15 as a white solid (709 mg, 48%): mp 138°-142° C.; Rf 0.65 (1:9 MeOH:CH2Cl2); 1H NMR (CDCl3) 7.98(d, 1H, J=6.39 Hz), 6.23(t, 1H, J=6.78 Hz), 4.49(dt, 1H, J=5.56 Hz), 3.98(m, 2H), 3.84(m, 1H), 2.26(m, 2H), 0.90(s, 9H), 0.10(s, 6H); IR (KBr) 3460, 3190, 3080, 3050, 2930, 2860, 1720, 1655, 1490, 1475, 1445, 1400, 1335, 1250, 1190, 1120, 1095, 1030, 1005, 950, 910, 835, 760, 700, 670, 640 cm-1 .

Workup

  1. customThe pyridine was removed under reduced pressure
  2. dissolutionthe residue dissolved in DMF (4 ml)
  3. stirringto stir overnight at room temperature
  4. customThe DMF was removed under pressure
  5. dissolutionthe residue was dissolved in 80% aqueous acetic acid (5 ml)
  6. temperatureto reflux for 30 min
  7. temperaturecooled
  8. customthe residue was purified by chromatography (1:1 EtOAc:hexanes)

Sources & evidence

ORD record
ord-07e54e5e30cc47cc91869f9217e98ec5
Source dataset
uspto-grants-1993_08
Patent number
US05233031

Reaction notes

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