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【结 构 式】 
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【分子编号】56044 【品名】gadolinium (2R)-2-{4,10-bis[(1R)-3-carboxy-1-carboxylatopropyl]-7-[(1R)-1-carboxy-4-hydroxy-4-oxobutyl]-1,4,7,10-tetraazacyclododecan-1-yl}-4-carboxybutanoate 【CA登记号】 |
【 分 子 式 】C28H41GdN4O16 【 分 子 量 】846.9009 【元素组成】C 39.71% H 4.88% Gd 18.57% N 6.62% O 30.23% |
合成路线1
该中间体在本合成路线中的序号：(V)Alkylation of tetraazacyclodecane (I) with ethyl 2-bromobutyrate (II) afforded the tetrasubstituted macrocycle (III) as a mixture of diastereoisomers. Subsequent hydrolysis of the ethyl ester groups of (III) using ethanolic NaOH gave the octacarboxylic acid (IV). Complexation of (IV) with either Gd2O3 or GdCl3 and NaOH generated the corresponding gadolinium chelate. The mixture of diastereoisomeric chelates was then isomerized under acidic conditions to furnish the racemic pair of R,R,R,R and S,S,S,S isomers (V).
| 【1】 Port, M.; et al.; P792: A rapid clearance blood pool agent for magnetic resonance imaging: Preliminary results. MAGMA Magn Reson Mater Phys Biol Med 2001, 12, 2-3, 121. |
| 【2】 Rousseaux, O.; Simonot, C. (Guerbet SA); Gadolinium complex tetramides and use in medical imaging. EP 1178975; FR 2793795; WO 0071526 . |
| 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) | 56041 | diethyl 2-bromopentanedioate | C9H15BrO4 | 详情 | 详情 | |
| (III) | 56042 | diethyl 2-{4,7,10-tris[4-ethoxy-1-(ethoxycarbonyl)-4-oxobutyl]-1,4,7,10-tetraazacyclododecan-1-yl}pentanedioate | C44H76N4O16 | 详情 | 详情 | |
| (IV) | 56043 | 2-[4,10-bis(1-carboxy-4-hydroxy-4-oxobutyl)-7-(1,3-dicarboxypropyl)-1,4,7,10-tetraazacyclododecan-1-yl]pentanedioic acid | C28H44N4O16 | 详情 | 详情 | |
| (V) | 56044 | gadolinium (2R)-2-{4,10-bis[(1R)-3-carboxy-1-carboxylatopropyl]-7-[(1R)-1-carboxy-4-hydroxy-4-oxobutyl]-1,4,7,10-tetraazacyclododecan-1-yl}-4-carboxybutanoate | C28H41GdN4O16 | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(V)Deprotection of the phthaloyl group of (XIV) by hydrazinolysis provided amine (XV). This was then coupled with the octaacid gadolinium chelate (V) in the presence of EDC and HOBt leading to the target amide.
| 【1】 Port, M.; et al.; P792: A rapid clearance blood pool agent for magnetic resonance imaging: Preliminary results. MAGMA Magn Reson Mater Phys Biol Med 2001, 12, 2-3, 121. |
| 【2】 Rousseaux, O.; Simonot, C. (Guerbet SA); Gadolinium complex tetramides and use in medical imaging. EP 1178975; FR 2793795; WO 0071526 . |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (V) | 56044 | gadolinium (2R)-2-{4,10-bis[(1R)-3-carboxy-1-carboxylatopropyl]-7-[(1R)-1-carboxy-4-hydroxy-4-oxobutyl]-1,4,7,10-tetraazacyclododecan-1-yl}-4-carboxybutanoate | C28H41GdN4O16 | 详情 | 详情 | |
| (XIV) | 56050 | 2,4,6-tribromo-5-{[2-({4-[(4-{[2-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)acetyl]amino}benzoyl)amino]benzoyl}amino)acetyl]amino}-N~1~,N~1~,N~3~,N~3~-tetrakis(2,3,4,5,6-pentahydroxyhexyl)isophthalamide | C58H72Br3N7O28 | 详情 | 详情 | |
| (XV) | 56051 | 5-[(2-{[4-({4-[(2-aminoacetyl)amino]benzoyl}amino)benzoyl]amino}acetyl)amino]-2,4,6-tribromo-N~1~,N~1~,N~3~,N~3~-tetrakis(2,3,4,5,6-pentahydroxyhexyl)isophthalamide | C50H70Br3N7O26 | 详情 | 详情 |