Imidazole → HCID 10451163, compound

Temperature

0 °C

To a solution of 5-fluoro-2′-deoxyuridine (FDUR) (4.92 g, 20 mmol) in pyridine (100 mL) was added DMTrCl (10.16 g, 30 mmol) portion-wise at 0° C. and the solution was stirred at 0° C. for 2 h. Water (5 mL) was added and the mixture was evaporated to dryness and the residue was co-evaporated with toluene (2×20 mL). The residue was dissolved in EtOAc (200 mL) and the solution was washed with brine and dried over Na2SO4. Solvent was removed and the residue was dissolved in CH2Cl2 (100 ml). To the solution were added imidazole (4.08 g, 60 mmol) then t-butyldimethylsilylchloride (TBSCl, 4.52 g, 30 mmol) and the mixture was stirred at room temperature for overnight. Water (50 mL) was added and the mixture was evaporated to dryness. The residue was dissolved in EtOAc (300 mL) and the solution was washed with brine and dried over Na2SO4. Solvent was removed and the residue was co-evaporated with toluene twice then dissolved in CH2Cl2 (200 mL). To the solution was added trifluoroacid (TFA, 3 mL) and the solution was stirred at room temperature for 3 h. Water (5 mL) was added and the mixture was stirred for 30 min then methanol (10 mL) added. After 10 min, the solution was neutralized with 30% ammonium hydroxide. The mixture was concentrated to dryness and the residue was purified by silica gel chromatography to give product as solid (5.6 g. 78%). 1H-NMR (CDCl3): δ 8.88 (br s, 1H), 7.96 (d, J=6.4 Hz, 1H), 6.23 (m, 1H), 4.78 (m, 1H), 3.95 (m, 1H), 3.79 (m, 1H), 2.28 (m, 2H), 0.88 (s, 9H), 0.00, 0.09 (ss, 6H). LC-MS (ESI): 361 [M+1]+.

1. customthe mixture was evaporated to dryness
2. dissolutionThe residue was dissolved in EtOAc (200 mL)
3. washthe solution was washed with brine
4. dry with materialdried over Na2SO4
5. customSolvent was removed
6. dissolutionthe residue was dissolved in CH2Cl2 (100 ml)
7. customthe mixture was evaporated to dryness
8. dissolutionThe residue was dissolved in EtOAc (300 mL)
9. washthe solution was washed with brine
10. dry with materialdried over Na2SO4
11. customSolvent was removed
12. dissolutiondissolved in CH2Cl2 (200 mL)
13. additionTo the solution was added trifluoroacid (TFA, 3 mL)
14. stirringthe solution was stirred at room temperature for 3 h
15. additionWater (5 mL) was added
16. stirringthe mixture was stirred for 30 min
17. additionmethanol (10 mL) added
18. waitAfter 10 min
19. concentrationThe mixture was concentrated to dryness
20. customthe residue was purified by silica gel chromatography

ORD record

ord-77ae350968444a3396bfaef110d52a49

Source dataset

uspto-grants-2015_10

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09156874B2