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【结 构 式】 
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【分子编号】69264 【品名】(3aS,11aR,12aS,14aS)-ethyl 2-((2-(4-isopropylthiazol-2-yl)-7-methoxy-8-methylquinolin-4-yl)oxy)-5-methyl-4,14-dioxo-1,2,3,3a,4,5,6,7,8,9,11a,12,12a,13,14,14a-hexadecahydrocyclopenta[c]cyclopropa[g][1,6]diazacyclotetradecine-12a-carboxylate 【CA登记号】 |
【 分 子 式 】C37H46N4O6S 【 分 子 量 】674.862 【元素组成】C 65.85% H 6.87% N 8.30% O 14.22% S 4.75% |
合成路线1
该中间体在本合成路线中的序号：(II)Ring closing metathesis of intermediate (I) by means of Hoveyda–Grubbs first-generation catalyst in 1,2-dichloroethane at 75 °C furnishes macrocycle (II), which is then treated with LiOH in THF/MeOH/H2O to give carboxylic acid (III). Finally, activation of acid (III) by treatment with 1,1’-carbonyldiimidazole (CDI) in refluxing THF affords the oxazolidinedione derivative (IV), which is readily reacted with cyclopropylsulfonamide (V) in the presence of DBU in THF at 50 °C .
| 【1】 Raboisson, P., De Kock, H., Rosenquist, A. et al. Structure-activity relationship study on a novel series of cyclopentane-containing macrocyclic inhibitors of the hepatitis C virus NS3/4A protease leading to the discovery of TMC435350. Bioorg Med Chem Lett 2008, 18(17): 4853-8. |
| 【2】 Stokbroekx, S.C.M., Leys, C., Swinney, K.A., Wuyts, S., Horvath, A. (Tibotec Pharmaceuticals Ltd.). Polymorphic forms of a macrocyclic inhibitor of HCV. WO 2008092954. |
| 【3】 Raboisson, P.J.-M.B., De Kock, H.A., Hu, L. et al. (Tibotec Pharmaceuticals Ltd.; Medivir AB). Macrocyclic inhibitors of hepatitis C virus. CA 2616580, EP 1912999, JP 2009502889, WO 2007014926. |
| 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) | 69263 | (1S,2R)-ethyl 1-((1S,2S,4S)-2-(hex-5-en-1-yl(methyl)carbamoyl)-4-((2-(4-isopropylthiazol-2-yl)-7-methoxy-8-methylquinolin-4-yl)oxy)cyclopentanecarboxamido)-2-vinylcyclopropanecarboxylate | C39H50N4O6S | 详情 | 详情 | |
| (II) | 69264 | (3aS,11aR,12aS,14aS)-ethyl 2-((2-(4-isopropylthiazol-2-yl)-7-methoxy-8-methylquinolin-4-yl)oxy)-5-methyl-4,14-dioxo-1,2,3,3a,4,5,6,7,8,9,11a,12,12a,13,14,14a-hexadecahydrocyclopenta[c]cyclopropa[g][1,6]diazacyclotetradecine-12a-carboxylate | C37H46N4O6S | 详情 | 详情 | |
| (III) | 69265 | (2R,11aS,12aR,14aR)-2-((2-(4-isopropylthiazol-2-yl)-7-methoxy-8-methylquinolin-4-yl)oxy)-5-methyl-4,14-dioxo-1,2,3,3a,4,5,6,7,8,9,11a,12,12a,13,14,14a-hexadecahydrocyclopenta[c]cyclopropa[g][1,6]diazacyclotetradecine-12a-carboxylic acid | C35H42N4O6S | 详情 | 详情 | |
| (IV) | 69266 | (1aS,11S,12aR,17aR)-11-((2-(4-isopropylthiazol-2-yl)-7-methoxy-8-methylquinolin-4-yl)oxy)-8-methyl-1,1a,5,6,7,8,10,11,12,12a-decahydrocyclopenta[c]cyclopropa[g]oxazolo[3,4-f][1,6]diazacyclotetradecine-9,13,15,17(4H,9aH)-tetraone | C36H40N4O7S | 详情 | 详情 | |
| (V) | 68242 | cyclopropanesulfonamide；Cyclopropanesulfonyl amide | 154350-29-5 | C3H7NO2S | 详情 | 详情 |