【结 构 式】 |
【分子编号】13569 【品名】4-Amino-1-[(2R,3R,4S,5R)-3,4-dihydroxy-5-methyltetrahydro-2-furanyl]-5-fluoro-2(1H)-pyrimidinone 【CA登记号】 |
【 分 子 式 】C9H12FN3O4 【 分 子 量 】245.2105032 【元素组成】C 44.08% H 4.93% F 7.75% N 17.14% O 26.1% |
合成路线1
该中间体在本合成路线中的序号:(I)The silylation of 5'-deoxy-5-fluorocytidine (I) with tert-butyldimethylsilyl chloride and imidazole in DMF gives 2'-O,3'-O-bis(tert-butyldimethylsilyl)-5'-deoxy-5-fluorocytidine (II), which is acylated with 3,4,5-trimethoxybenzoyl chloride (III) and dimethylaminopyridine in dichloromethane to afford 2'-O,3'-O-bis(tert-butyldimethylsilyl)-5'-deoxy-5-fluoro-N4-(3,4,5-trimethoxybenzoyl)cytidine (IV). Finally, this compound is deprotected with tetrabutylammonium fluoride in THF.
【1】 Fujiu, M.; Ishitsuka, H.; Miwa, M.; Umeda, I.; Yokose, K. (F. Hoffmann-La Roche AG); Fluorocytidine derivs., their preparation and medical preparations containing them. AU 8825168; EP 0316704; JP 1989153696; US 4966891 . |
【2】 Hoshi, A.; Castaner, J.; Galocitabine. Drugs Fut 1993, 18, 4, 316. |
中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
---|---|---|---|---|---|---|
(I) | 13569 | 4-Amino-1-[(2R,3R,4S,5R)-3,4-dihydroxy-5-methyltetrahydro-2-furanyl]-5-fluoro-2(1H)-pyrimidinone | C9H12FN3O4 | 详情 | 详情 | |
(II) | 13570 | 4-Amino-1-((2R,3R,4R,5R)-3,4-bis[[tert-butyl(dimethyl)silyl]oxy]-5-methyltetrahydro-2-furanyl)-5-fluoro-2(1H)-pyrimidinone | C21H40FN3O4Si2 | 详情 | 详情 | |
(III) | 13571 | 3,4,5Ttrimethoxybenzoyl chloride | 4521-61-3 | C10H11ClO4 | 详情 | 详情 |
(IV) | 13572 | N-[1-((2R,3R,4R,5R)-3,4-Bis[[tert-butyl(dimethyl)silyl]oxy]-5-methyltetrahydro-2-furanyl)-5-fluoro-2-oxo-1,2-dihydro-4-pyrimidinyl]-3,4,5-trimethoxybenzamide | C31H50FN3O8Si2 | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号:(I)The acetylation of 5'-deoxy-5-fluorocytidine (I) with acetic anhydride in dry pyridine gives 2',3'-di-O-acetyl-5'-deoxy-5-fluorocytidine (II), which is condensed with pentyl chloroformate (III) by means of pyridine in dichromethane yielding 2',3'-di-O-acetyl-5'-deoxy-5-fluoro-N4-(pentyloxycarbonyl)cytidine (IV). Finally, this compound is deacetylated with NaOH in dichloromethane/water. The diacetylated cytidine (II) can also be obtained by condensation of 5-fluorocytosine (V) with 1,2,3-tri-O-acetyl-5-deoxy-beta-D-ribofuranose (VI) by means of trimethylchlorosilane in acetonitrile or HMDS and SnCl4 in dichloromethane..
【1】 Hoshi, A.; Castañer, J.; Capecitabine. Drugs Fut 1996, 21, 4, 358. |
【2】 Arasaki, M.; Ishitsuka, H.; Kurama, I.; Miwa, M.; Murasaki, C.; Shimma, N.; Umeda, I. (F. Hoffmann-La Roche AG); N-Oxycarbonyl substd. 5'-deoxy-5-fluorocytidines. EP 0602454; JP 1994211891; US 5472949 . |
【3】 Arasaki, M.; Shimma, N.; Umeda, I.; et al.; The design and synthesis of a new tumor-selective fluoropyrimidine carbamate, capecitabine. Bioorg Med Chem Lett 2000, 8, 7, 1697. |
中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
---|---|---|---|---|---|---|
(I) | 13569 | 4-Amino-1-[(2R,3R,4S,5R)-3,4-dihydroxy-5-methyltetrahydro-2-furanyl]-5-fluoro-2(1H)-pyrimidinone | C9H12FN3O4 | 详情 | 详情 | |
(II) | 16744 | (2R,3R,4R,5R)-4-(acetoxy)-2-[4-amino-5-fluoro-2-oxo-1(2H)-pyrimidinyl]-5-methyltetrahydro-3-furanyl acetate | 161599-46-8 | C13H16FN3O6 | 详情 | 详情 |
(III) | 16745 | 1-[(chlorocarbonyl)oxy]pentane | 638-41-5 | C6H11ClO2 | 详情 | 详情 |
(IV) | 16746 | (2R,3R,4R,5R)-4-(acetoxy)-2-[5-fluoro-2-oxo-4-[[(pentyloxy)carbonyl]amino]-1(2H)-pyrimidinyl]-5-methyltetrahydro-3-furanyl acetate | 162204-20-8 | C19H26FN3O8 | 详情 | 详情 |
(V) | 16747 | 4-amino-5-fluoro-2(1H)-pyrimidinone; 5-fluorocytosine | 2022-85-7 | C4H4FN3O | 详情 | 详情 |
(VI) | 16748 | (2R,3R,4R,5S)-4,5-bis(acetoxy)-2-methyltetrahydro-3-furanyl acetate | 62211-93-2 | C11H16O7 | 详情 | 详情 |