Studies on antitumor agents. IX. Synthesis of 3'-O-benzyl-2'-deoxy-5-trifluoromethyluridine.
A practical synthesis of 3'-O-benzyl-2'-deoxy-5-trifluoromethyluridine (1), a candidate antitumor agent for clinical testing, was developed from 2'-deoxy-5-iodouridine (3). Benzylation of 2'-deoxy-5-iodo-5'-O-trityluridine (14) with benzyl bromide and sodium hydride in tetrahydrofuran gave the 3'-O-derivative (16). Benzoylation of 16 afforded the N3-benzoyl derivative (17). Coupling of 17 with trifluoromethylcopper, prepared from bromotrifluoromethane and copper powder in the presence of 4-dimethylaminopyridine, gave the 5-trifluoromethyl derivative (19) minimally contaminated with the 5-pentafluoroethyl compound. Deprotection of 19 furnished 1.
Yamashita
J
J
Matsumoto
H
H
Kobayashi
K
K
Noguchi
K
K
Yasumoto
M
M
Ueda
T
T
D000970:Antineoplastic Agents / Q000138:chemical synthesis*; D055598:Chemical Phenomena; D002621:Chemistry; D013936:Thymidine / Q000031:analogs & derivatives*; D014271:Trifluridine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology
D000970:Antineoplastic Agents; C062357:3'-O-benzyl-2'-deoxy-5-trifluoromethyluridine; D014271:Trifluridine; D013936:Thymidine