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【结 构 式】 
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【分子编号】59311 【品名】5-(acetylamino)-N~1~,N~3~-bis(2,3-dihydroxypropyl)-2,4,6-triiodoisophthalamide 【CA登记号】 |
【 分 子 式 】C16H20I3N3O7 【 分 子 量 】747.06423 【元素组成】C 25.72% H 2.7% I 50.96% N 5.62% O 14.99% |
合成路线1
该中间体在本合成路线中的序号：(II)Acetylation of 5-amino-N,N'-bis(2,3-dihydroxypropyl)-2,4,6-triiodoisophthalamide (I) in refluxing acetic anhydride in the presence of p-toluenesulfonic acid affords acetamide (II). The title compound is then obtained by alkylation of acetamide (II) with 1-chloro-3-methoxy-2-propanol (III). The selectivity in the alkylation at the acetamide N has been improved with the addition of several metallic cations, the best results being obtained with calcium ions.
| 【1】 Bjoersvik, H.-R.; et al.; An observation of cationic influence on the N/O alkylation selectivity in the alkylation of a compound containing several nucleophilic sites. Acta Chem Scand 1994, 48, 7, 582. |
| 【2】 Wille, K. (Amersham plc); X-Ray contrast agents. EP 0105752 . |
| 【3】 Cockbain, J.R.M.; Gulbrandsen, T.; Ingvoldstad, O.E.; Holmaas, L.T. (Amersham plc); Process for the preparation of contrast agents. WO 9808805 . |
| 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) | 59316 | 5-amino-N~1~,N~3~-bis(2,3-dihydroxypropyl)-2,4,6-triiodoisophthalamide | C14H18I3N3O6 | 详情 | 详情 | |
| (II) | 59311 | 5-(acetylamino)-N~1~,N~3~-bis(2,3-dihydroxypropyl)-2,4,6-triiodoisophthalamide | C16H20I3N3O7 | 详情 | 详情 | |
| (III) | 34214 | 1-chloro-3-methoxy-2-propanol | 4151-97-7 | C4H9ClO2 | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(I)In an improved method, the acetamido isophthalamide (I) is treated with boric acid and KOH to form the cyclic diborate tripotassium salt (II). Subsequent alkylation of (II) with 1-chloro-3-methoxy-2-propanol (III) yields regioselectively the N-alkylated acetamide (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 . |
合成路线3
该中间体在本合成路线中的序号：(I)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4
该中间体在本合成路线中的序号：(I)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 . |