反应详情

Crude intermediate 10 was used for preparation of the appropriately protected cytidine phosphoramidite 2c as shown in Scheme VI below. The uracil base of 10 was converted to cytosine by adaptation of the method of Divakar and Reese, J. Chem. Soc., Perkin. Trans. 1 1982, 1171-1176. Subsequent 4-N benzoylation and reduction of the 3'-azido to an amino group gave compound 13, which was separable from its regioisomer by silica gel chromatography. Protection of the 3'-amine with an MMT group, followed by selective 5'-O-debenzoylation produced intermediate 15. Subsequent 5'-phosphitylation lead to desired phosphoramidite 2c in a 10% overall yield based on anhydronucleoside 8. ##STR12## More particularly, the steps were carried out as follows: N4,5'-O-dibenzoyl-2'-fluoro-3'-amino-2',3'-dideoxycytidine 13 was prepared as follows: To 6.9 g (18.4 mmol) of crude 10 (containing 35% 10i) in 50 mL anhydrous CH3CN was added an ice-cold solution of 11.7 g (169 mmol) 1,2,4-triazole and 3.35 mL (36.1 mmol) POCl3 in 90 mL anhydrous CH3CN. The mixture was cooled in an ice bath and anhydrous triethylamine (23 mL, 165 mmol) was added, then the reaction allowed to warm to room temperature with stirring. After 90 min, 15 mL (108 mmol) triethylamine and 4 mL water were added and the mixture stirred for 10 min. The solvent was removed in vacuo, then 250 mL ethyl acetate was added, and the solution was TLC indicated a fluorescent intermediate with the same mobility as the starting material.