Reacción #444172

Ecuación de reacción

5,6-dichlorobenzimidazole

2'-Deoxy-2'-fluorouridine

5,6-dichlorobenzimidazole

→

compound 15

Rendimiento 67.0%

5,6-Dichloro-1-(2-deoxy-2-fluoro-β-D-ribofuranosyl)benzimidazole

Rendimiento 67.0%

Disolventes

citrate

Condiciones de reacción

Tratamiento posterior

1. 1
   workup.ADDITIONwas added
2. 2
   Otrowas placed in a 50° C.
3. 3
   workup.ADDITIONN-deoxyribo-furanosyl transferase (60,000 units; see Cook et al., 1990) was added
4. 4
   workup.WAITthe reaction continued for 2 days
5. 5
   OtroThe enzyme was precipitated
6. 6
   Temperaturaby cooling to room temperature
7. 7
   workup.ADDITIONCelite® (50-60 g) was added
8. 8
   Filtraciónthe reaction mixture filtered
9. 9
   ExtracciónThe product was extracted with ethyl acetate (3×)
10. 10
    OtroThe ethyl acetate was removed in vacuo
11. 11
    Otrothe residue purified by chromatography on 75 g of basic alumina
12. 12
    Lavadoeluted with chloroform/methanol (95:5
13. 13
    workup.ADDITIONThe product containing fractions
14. 14
    Otrothe solvents removed in vacuo

Procedimiento

2'-Deoxy-2'-fluorouridine, compound 13 (0.99 g, 4 mmol), which can be prepared by the method of Codington et al. (Codington et al., 1968), was dissolved in 800 mL of 50 mM pH 6.0 citrate buffer. 5,6-dichlorobenzimidazole, compound 14 (0.30g, 1.6 mmoles), which can be prepared by the method of Townsend et al. (Townsend et al., 1970), was added and the reaction was placed in a 50° C. water bath. N-deoxyribo-furanosyl transferase (60,000 units; see Cook et al., 1990) was added and the reaction mixture was gently shaken overnight. 5,6-dichlorobenzimidazole, compound 14 (0.30 g, 1.6 mmoles) was added and the reaction continued for 2 days. The enzyme was precipitated by heating to 80° C. followed by cooling to room temperature. Celite® (50-60 g) was added and the reaction mixture filtered. The product was extracted with ethyl acetate (3×). The ethyl acetate was removed in vacuo and the residue purified by chromatography on 75 g of basic alumina eluted with chloroform/methanol (95:5, v/v) followed by (9:1, v/v), then (2:1, v/v), and finally (1:1, v/v). The product containing fractions were combined and the solvents removed in vacuo to give 0.54 g (67%) of compound 15.

Fuente