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【结 构 式】 
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【药物名称】Iodixanol, DU-6807, 2-5410-3A, OptiPrep, Visipaque, Acupaque 【化学名称】5,5'-[(2-Hydroxytrimethylene)bis(acetylimino)]bis[N,N/1-bis(2,3-dihydroxypropyl)-2,4,6-triiodoisophthalamide 【CA登记号】92339-11-2 【 分 子 式 】C35H44I6N6O15 【 分 子 量 】1550.19853 |
【开发单位】Amersham Health (Originator), Daiichi Pharmaceutical (Licensee) 【药理作用】Contrast Mediums, DIAGNOSTIC AGENTS |
合成路线1
The title compound is prepared by condensation of the acetamido isophthalamide (I) with epichlorohydrin (II) in 2-methoxyethanol.
| 【1】 Wille, K.; Hansen, P.-E.; Holtermann, H. (Amersham plc); X-ray contrast agents. EP 0108638; US 5349085 . |
| 【2】 Cockbain, J.; Malthe-Soerenssen, D.; Schelver Hyni, A.C.; Aabye, A.; Bjoersvik, H.R.; Brekke, G.; Sjoegren, C.E. (Amersham plc); Process for the production of iodinated organic X-ray contrast agents. WO 9823296 . |
| 【3】 Skailes, H.J.; Homestad, O.M. (Amersham plc); Preparation of iodixanol. WO 0047549 . |
合成路线2
In an alternative method, the tetra-acid chloride (I) derived from O-acetyl-iodixanol is condensed with 3-amino-1,2-propanediol (II) under Schotten-Baumann conditions to afford amide (III). The acetate ester group of (III) is then removed by acidic hydrolysis to furnish the title compound.
| 【1】 Bjoersvik, H.-R.; et al.; N-acylation reactions performed in aqueous reaction medium: Screening and optimising of a synthetic step of a process for iodixanol. Org Process Res Dev 2002, 6, 2, 113. |
| 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) | 59312 | 2-[acetyl-3,5-bis(chlorocarbonyl)-2,4,6-triiodoanilino]-1-{[acetyl-3,5-bis(chlorocarbonyl)-2,4,6-triiodoanilino]methyl}ethyl acetate | C25H14Cl4I6N2O8 | 详情 | 详情 | |
| (II) | 12979 | 3-Amino-1,2-propanediol；3-aminopropane-1,2-diol | 616-30-8 | C3H9NO2 | 详情 | 详情 |
| (III) | 59313 | 2-(acetyl-3,5-bis{[(2,3-dihydroxypropyl)amino]carbonyl}-2,4,6-triiodoanilino)-1-[(acetyl-3,5-bis{[(2,3-dihydroxypropyl)amino]carbonyl}-2,4,6-triiodoanilino)methyl]ethyl acetate | C37H46I6N6O16 | 详情 | 详情 |
合成路线3
In a different strategy, the acetamido isophthalamide (I) is treated with boric acid and KOH to form the cyclic diborate tripotassium salt (II). Subsequent condensation of (II) with epichlorohydrin (III) yields the dimeric adduct (IV). The borate groups of (IV) are finally removed upon quenching with diluted HCl.
| 【1】 Bjoersvik, H.-R.; et al.; A selective process for N-alkylation in competition with O-alkylation: Boric acid, borax, and metaborate as a cheap and effective protecting group applicable for industrial-scale synthetic processes. Org Process Res Dev 2001, 5, 5, 472. |
| 【2】 Priebe, H. (Amersham plc); An N-alkylation. GB 2331098 . |