|
【结 构 式】 
|
【分子编号】12213 【品名】[(2R,3R,4R,5R)-3-(acetoxy)-4-bromo-5-[5-methyl-2,4-dioxo-3,4-dihydro-1(2H)-pyrimidinyl]tetrahydro-2-furanyl]methyl acetate 【CA登记号】 |
【 分 子 式 】C14H17BrN2O7 【 分 子 量 】405.20226 【元素组成】C 41.5% H 4.23% Br 19.72% N 6.91% O 27.64% |
合成路线1
该中间体在本合成路线中的序号：(XVIII)6) Another route involves acetylation of the anhydro derivative (XVI) to give (XVII), which is converted to (XVIII) by treatment with sodium bromide in sulfuric acid and submitted to elimination with zinc and sodium hydroxide.
| 【1】 Ikeda, T.; Asamura, K. (Yamasa Shoyu Co., Ltd.); Process for producing 1-(2,3-dideoxy-beta-D-glycero-pent-enofuranosyl)thymine. WO 9209599 . |
| 【2】 Robinson, C.; Castaner, J.; Stavudine. Drugs Fut 1994, 19, 10, 925. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (XVI) | 12211 | (2R,3R,3aS,9aR)-3-Hydroxy-2-(hydroxymethyl)-7-methyl-2,3,3a,4a,5,9a-hexahydro-6H-furo[2',3':4,5][1,3]oxazolo[3,2-a]pyrimidin-6-one | C10H14N2O5 | 详情 | 详情 | |
| (XVII) | 12212 | (2R,3R,3aS,9aR)-2-[(acetoxy)methyl]-7-methyl-6-oxo-2,3,3a,5,6,9a-hexahydro-4aH-furo[2',3':4,5][1,3]oxazolo[3,2-a]pyrimidin-3-yl acetate | C14H18N2O7 | 详情 | 详情 | |
| (XVIII) | 12213 | [(2R,3R,4R,5R)-3-(acetoxy)-4-bromo-5-[5-methyl-2,4-dioxo-3,4-dihydro-1(2H)-pyrimidinyl]tetrahydro-2-furanyl]methyl acetate | C14H17BrN2O7 | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(XLV)Condensation of the bicyclic oxazoline (XV) with 2-(chloromethyl)acrylic acid ethyl ester (XLI) - obtained by treatment of the hydroxymethyl analogue (XLII) with SOCl2 - in dimethylacetamide gives the aduct (XLIII), which is treated first with hydroquinone and Na2CO3 in water and then with H2 over Pd/Al2O3 in the same solvent to provide 2,2'-anhydro-b-L-thymidine (XLIV). Reaction of compound (XLIV) with acetyl bromide in DMF/AcOEt yields 2'-bromo-3',5'-di-O-acetyl-b-L-thymidine (XLV), which is debrominated with H2 over Pd/Al2O3.to afford the 2'-deoxynucleoside (XLVI). Finally, this compound is deacetylated by means of NH3 in MeOH.
| 【1】 Sorbera, L.A.; Castañer, J.; Castañer, R.M.; Bayes, M.; Telbivudine. Drugs Fut 2003, 28, 9, 870. |
| 【2】 Suzuki, T.; Iizuka, H.; Togashi, K. (Mitsui Chemicals, Inc.); L-Nucleic acid derivs. and processes for the synthesis thereof. EP 1348712; JP 2002241390; WO 0244194 . |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (XV) | 56918 | (3aS,5S,6S,6aR)-5-(hydroxymethyl)-2-iminohexahydrofuro[2,3-d][1,3]oxazol-6-ol | C6H10N2O4 | 详情 | 详情 | |
| (XLI) | 62924 | ethyl 2-(chloromethyl)acrylate | C6H9ClO2 | 详情 | 详情 | |
| (XLII) | 11327 | ethyl 2-(hydroxymethyl)acrylate | 10029-04-6 | C6H10O3 | 详情 | 详情 |
| (XLIII) | 62923 | ethyl 2-{[(3aS,5S,6S,6aR)-6-hydroxy-5-(hydroxymethyl)-2-iminotetrahydrofuro[2,3-d][1,3]oxazol-3(2H)-yl]methyl}acrylate | C12H18N2O6 | 详情 | 详情 | |
| (XLIV) | 62927 | (2S,3S,3aR,9aS)-3-hydroxy-2-(hydroxymethyl)-7-methyl-2,3,3a,9a-tetrahydro-6H-furo[2',3':4,5][1,3]oxazolo[3,2-a]pyrimidin-6-one | C10H12N2O5 | 详情 | 详情 | |
| (XLV) | 12213 | [(2R,3R,4R,5R)-3-(acetoxy)-4-bromo-5-[5-methyl-2,4-dioxo-3,4-dihydro-1(2H)-pyrimidinyl]tetrahydro-2-furanyl]methyl acetate | C14H17BrN2O7 | 详情 | 详情 | |
| (XLVI) | 62928 | {(2S,3R,5S)-3-(acetyloxy)-5-[5-methyl-2,4-dioxo-3,4-dihydro-1(2H)-pyrimidinyl]tetrahydro-2-furanyl}methyl acetate | C14H18N2O7 | 详情 | 详情 |