RVT, DPC-817, beta-D-D4FC, D-D4FC, Reverset

5-氟-1-(2',3'-二脱氧-2',3'-二脱氢β-D-呋喃阿糖基)-胞嘧啶(Dexelvucitabine) Chemical Name: beta-D-2',3'-Didehydro-2',3'-dideoxy-5-fluorocytidine
CAS No. 181785-83-1, 134379-77-4 (undefined isomer)
项目整合开发状态: Phase II
项目研究机构: Bristol-Myers Squibb (Originator), Incyte (Licensee), Pharmasset (Codevelopment)
合成路线:The bromoacetylation of 5-fluorocytidine (I) with 2-acetoxyisobutyryl bromide (II) in acetonitrile,ethyl acetate or dichloromethane gives a mixture of two bromoacylated compounds (III) and (IV),with minor amounts of two other compounds (V) and (VI) that are separated by chromatography.The mixture of (III) and (IV),without separation,is treated with Zn/Cu in DMF or methanol/ethyl acetate to yield the unsaturated cytidine derivative (VII),which is finally deacylated by means of Na-OMe in methanol to afford the target fluorocytidine derivative.

合成路线:The bromoacetylation of 5-fluorouridine (I) with 2-acetoxyisobutyryl bromide (II) in acetonitrile,ethyl acetate or dichloromethane gives a mixture of four bromoacylated compounds (III),(IV),(V) and (VI).This mixture,without separation,is treated with Zn/Ac-OH in DMF or methanol/ethyl acetate to yield two unsaturated uridine derivatives (VII) and (VIII),which are easily separated.The major isomer (VIII) is condensed with 1,2,4-triazole (IX) by means of POCl3 and TEA in acetonitrile to afford the triazolyl derivative (X),which is treated with ammonia in methanol to provide the cytidine derivative (XI).Finally,this compound is deacylated by means of NaOMe in methanol to afford the target fluorocytidine derivative.