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【结 构 式】 
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【分子编号】14860 【品名】tert-butyl 2-[4,10-bis[2-(tert-butoxy)-2-oxoethyl]-7-formyl-1,4,7,10-tetraazacyclododecan-1-yl]acetate 【CA登记号】 |
【 分 子 式 】C27H50N4O7 【 分 子 量 】542.71676 【元素组成】C 59.75% H 9.29% N 10.32% O 20.64% |
合成路线1
该中间体在本合成路线中的序号：(VI)The synthesis of gadoteridol is as follows: Compound (I) was reacted with DMF dimethylacetal to form the tricyclic intermediate (II). Following partial hydrolysis of (II), (III) was obtained and isolated in high quality and yield. (III) was reacted with tert-butyl bromoacetate in a basic media to obtain (IV), which was treated with aqueous sulfuric acid to effect removal of the tert-butyl and formyl protecting groups. (V) could be either crystallized or lyophilized. (V) was reacted with propylene oxide at pH 12 and excess propylene oxide was removed under vacuum upon completion of the reaction. (VI) was isolated by anion exchange chromatography with sulfate, and sulfate was then removed using a poly(4-vinylpyridine) resin. HP-DO3A was reacted with gadolinium oxide in water. Following concentration, excess gadolinium oxide was removed by filtration, and Gd(HP-DO3A)H2O was isolated by removing solvent. The product was then crystallized from methanol/acetone.
| 【1】 Emswiler, J.E.; Gaughan, G.T.; Delaney, E.J.; Prasad, J.S.; Tweedle, M.F.; Dischino, D.D.; Srivastava, S.K.; Synthesis of nonionic gadolinium chelates useful as contrast agents for magnetic resonance imaging: 1,4,7 Tris(carboxymethyl)-10-substituted-1,4,7,10-tetraazacyclodecanes and their corresponding gadolinium chelates. Inorg Chem 1991, 30, 6, 1265-9. |
| 【2】 Runge, V.M.; Tweedle, M.F.; Gadoteridol. Drugs Fut 1992, 17, 3, 187. |
| 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) | 14855 | 1,4,7,10-tetraazacyclododecane; Cyclen | 294-90-6 | C8H20N4 | 详情 | 详情 |
| (II) | 14856 | octahydro-5H-2a,4a,7,9a-tetraazacycloocta[cd]pentalene | C9H18N4 | 详情 | 详情 | |
| (III) | 14857 | 1,4,7,10-tetraazacyclododecane-1-carbaldehyde | C9H20N4O | 详情 | 详情 | |
| (IV) | 14858 | 2-[4,10-bis(2-hydroxy-2-oxoethyl)-7-(2-hydroxypropyl)-1,4,7,10-tetraazacyclododecan-1-yl]acetic acid | C17H32N4O7 | 详情 | 详情 | |
| (V) | 14859 | 2-[4,10-bis(2-hydroxy-2-oxoethyl)-1,4,7,10-tetraazacyclododecan-1-yl]acetic acid | C14H26N4O6 | 详情 | 详情 | |
| (VI) | 14860 | tert-butyl 2-[4,10-bis[2-(tert-butoxy)-2-oxoethyl]-7-formyl-1,4,7,10-tetraazacyclododecan-1-yl]acetate | C27H50N4O7 | 详情 | 详情 |