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【结 构 式】 
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【分子编号】31156 【品名】benzyl 2,2,2-trichloroethanimidoate 【CA登记号】81927-55-1 |
【 分 子 式 】C9H8Cl3NO 【 分 子 量 】252.52676 【元素组成】C 42.81% H 3.19% Cl 42.12% N 5.55% O 6.34% |
合成路线1
该中间体在本合成路线中的序号：(III)The benzoylation of 2'-deoxy-5-iodouridine (I) with benzoyl chloride by means of pyridine in dichloromethane gives 5'-O-benzoyl-2'-deoxy-5-iodouridine (II), which is treated with benzyl trichloroacetimidate (III) and trifluoromethanesulfonic acid in dichloromethane - THF to afford the 3'-O-benzyl derivative (IV). The hydrolysis of (IV) with sodium ethoxide in ethanol yields 3'-O-benzyl-2'-deoxy-5-iodouridine (V), which is finally trifluoromethylated with bromotrifluoromethane and copper in pyridine-DMF by means of dimethylaminopyridine. The tritylation of 2'-deoxyuridine (IX) with trityl chloride in hot pyridine gives 2'-deoxy-5'-O-trityluridine (X), which is benzylated with benzyl chloride and NaH in THF yielding 3'-O-benzyl-2'-deoxy-5'-O-trityluridine (XI). The photochemical trifluoromethylation of (XI) with N-nitroso-N-(trifluoromethyl)trifluoromethanesulfonamide and biacetyl in acetonitrile irradiated with a high-pressure Hg lamp in a glass tube at room temperature affords 3'-O-benzyl-2'-deoxy-5-(trifluoromethyl-5'-O-trityluridine (XII), which is finally deprotected with HCl in methanol.
| 【1】 Fujii, S.; Yamashita, J.; Matsumoto, H.; Takeda, S.; Terada, T.; Yasumoto, M.; Unemi, N. (Taiho Pharmaceutical Co., Ltd.); Novel 2'-deoxy-5-substd. uridine derivs., processes for preparing the same and antitumor agent containing the same. EP 0129984; ES 8606381; ES 8606382; ES 8607982; ES 8706715; JP 1984216899; JP 1985061591 . |
| 【2】 Yasumoto, M.; Matsumoto, H.; Tada, Y.; Kobayashi, K.; Noguchi, K. (Taiho Pharmaceutical Co., Ltd.); Method for the preparation of 3'-O-benzyl-2'-deoxy-beta-uridines. JP 1987187484 . |
| 【3】 Yamashita, J.-I.; Takeda, S.; Matsumoto, H.; Unemi, N.; Yasumoto, M.; Studies on antitumor agents. 8. Antitumor activities of O-alkyl derivatives of 2'-deoxy-5-(trifluoromethyl)uridine and 2'-deoxy-5-fluorouridine. J Med Chem 1989, 32, 1, 136-139. |
| 【4】 Hoshi, A.; Prous, J.; Castaner, J.; FTC-092. Drugs Fut 1990, 15, 8, 790. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| 10463 | Benzoyl chloride | 98-88-4 | C7H5ClO | 详情 | 详情 | |
| 19171 | 1-(Chloromethyl)benzene; Benzyl chloride | 100-44-7 | C7H7Cl | 详情 | 详情 | |
| (I) | 31154 | 1-[(2R,4S,5R)-4-hydroxy-5-(hydroxymethyl)tetrahydro-2-furanyl]-5-iodo-2,4(1H,3H)-pyrimidinedione | 54-42-2 | C9H11IN2O5 | 详情 | 详情 |
| (II) | 31155 | [(2R,3S,5R)-3-hydroxy-5-[5-iodo-2,4-dioxo-3,4-dihydro-1(2H)-pyrimidinyl]tetrahydro-2-furanyl]methyl benzoate | C16H15IN2O6 | 详情 | 详情 | |
| (III) | 31156 | benzyl 2,2,2-trichloroethanimidoate | 81927-55-1 | C9H8Cl3NO | 详情 | 详情 |
| (IV) | 31157 | [(2R,3S,5R)-3-(benzyloxy)-5-[5-iodo-2,4-dioxo-3,4-dihydro-1(2H)-pyrimidinyl]tetrahydro-2-furanyl]methyl benzoate | C23H21IN2O6 | 详情 | 详情 | |
| (V) | 31158 | 1-[(2R,4S,5R)-4-(benzyloxy)-5-(hydroxymethyl)tetrahydro-2-furanyl]-5-iodo-2,4(1H,3H)-pyrimidinedione | C16H17IN2O5 | 详情 | 详情 | |
| (IX) | 11875 | 1-[(2R,4S,5R)-4-Hydroxy-5-(hydroxymethyl)tetrahydro-2-furanyl]-2,4(1H,3H)-pyrimidinedione; 2'-Deoxyuridine | 951-78-0 | C9H12N2O5 | 详情 | 详情 |
| (X) | 31159 | 1-[(2R,4S,5R)-4-hydroxy-5-[(trityloxy)methyl]tetrahydro-2-furanyl]-2,4(1H,3H)-pyrimidinedione | C28H26N2O5 | 详情 | 详情 | |
| (XI) | 31160 | 1-[(2R,4S,5R)-4-(benzyloxy)-5-[(trityloxy)methyl]tetrahydro-2-furanyl]-2,4(1H,3H)-pyrimidinedione | C35H32N2O5 | 详情 | 详情 | |
| (XII) | 31161 | 1-[(2R,4S,5R)-4-(benzyloxy)-5-[(trityloxy)methyl]tetrahydro-2-furanyl]-5-(trifluoromethyl)-2,4(1H,3H)-pyrimidinedione | C36H31F3N2O5 | 详情 | 详情 |