【结 构 式】 |
【分子编号】59325 【品名】2-[[2-(acetyloxy)acetyl]-3,5-bis({[2,3-bis(acetyloxy)propyl]amino}carbonyl)-2,4,6-triiodoanilino]ethyl acetate 【CA登记号】 |
【 分 子 式 】C30H36I3N3O15 【 分 子 量 】1059.34047 【元素组成】C 34.01% H 3.43% I 35.94% N 3.97% O 22.65% |
合成路线1
该中间体在本合成路线中的序号:(XI)Chlorination of 5-amino-2,4,6-triiodoisophthalic acid (I) with SOCl2 in EtOAc or toluene affords acid chloride (II). Yields have been improved with the addition of benzyltriethylammonium chloride as a catalyst. Acid chloride (II) is then condensed with 3-amino-1,2-propanediol (III) to produce diamide (IV). Compound (IV) is converted to the tetraacetate ester (V) employing acetic anhydride in pyridine. Subsequent acylation of the amino group of (V) with acetoxyacetyl chloride (VI) gives amide (VII). After saponification of the ester groups of (VII), the resultant hydroxy acetamide (VIII) is alkylated by 2-chloroethanol (IX) to furnish the title compound. Alternatively, amide (VIII) is alkylated by bromoethyl acetate (X), producing (XI). Hexa-ester (XI) is finally hydrolyzed with aqueous sulfuric acid. An improved procedure for this final hydrolysis step uses 1,1,2-trichloroethane as co-solvent.
【1】 Lin, Y. (Mallinckrodt Medical Inc.); Cpds. suitable for X-ray visualisation methods. EP 0083964; US 4396598 . |
【2】 Dunn, T.J.; White, D.H.; Kneller, M.T.; Jones, M.M.; Doran, N.O. III; Bailey, A.R. (Mallinckrodt Medical Inc.); Process for producing ioversol. WO 9727172 . |
【3】 Kneller, M.T.; Bailey, A.R.; Sathe, S.S.; Spears, A.T.; Wisneski, R.C. (Mallinckrodt Medical Inc.); Improved synthesis of ioversol. WO 9323365 . |
【4】 Villa, M.; Castaldi, G.; Pozzoli, C.; Russo, L. (Zambon Group SpA); Process for the preparation of 5-amino-2,4,6-triiodoisophthalic acid dichloride by chlorination with thionyl chloride in the presence of a catalyst. WO 9636590 . |
【5】 Lin, Y.; Dean, R.T.; Kneller, M.; Wallace, R.A.; McCarthy, W.Z.; White, D.H. (Mallinckrodt Medical Inc.); Process for production of ioversol. WO 9111431 . |
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) | 22006 | 5-amino-2,4,6-triiodoisophthalic acid | 35453-19-1 | C8H4I3NO4 | 详情 | 详情 |
(II) | 31194 | 5-amino-2,4,6-triiodoisophthaloyl dichloride | 37441-29-5 | C8H2Cl2I3NO2 | 详情 | 详情 |
(III) | 12979 | 3-Amino-1,2-propanediol;3-aminopropane-1,2-diol | 616-30-8 | C3H9NO2 | 详情 | 详情 |
(IV) | 59316 | 5-amino-N~1~,N~3~-bis(2,3-dihydroxypropyl)-2,4,6-triiodoisophthalamide | C14H18I3N3O6 | 详情 | 详情 | |
(V) | 59322 | 2-(acetyloxy)-1-({[3-amino-5-({[2,3-bis(acetyloxy)propyl]amino}carbonyl)-2,4,6-triiodobenzoyl]amino}methyl)ethyl acetate | C22H26I3N3O10 | 详情 | 详情 | |
(VI) | 10456 | Acetoxiacetil chloride; 2-chloro-2-oxoethyl acetate | 13831-31-7 | C4H5ClO3 | 详情 | 详情 |
(VII) | 59323 | 2-(acetyloxy)-1-({[3-{[2-(acetyloxy)acetyl]amino}-5-({[2,3-bis(acetyloxy)propyl]amino}carbonyl)-2,4,6-triiodobenzoyl]amino}methyl)ethyl acetate | C26H30I3N3O13 | 详情 | 详情 | |
(VIII) | 59324 | N~1~,N~3~-bis(2,3-dihydroxypropyl)-5-(glycoloylamino)-2,4,6-triiodoisophthalamide | C16H20I3N3O8 | 详情 | 详情 | |
(IX) | 33463 | 2-bromoethyl acetate | 927-68-4 | C4H7BrO2 | 详情 | 详情 |
(X) | 10384 | 2-Chloro-1-ethanol; Ethylene chlorohydrin | 107-07-3 | C2H5ClO | 详情 | 详情 |
(XI) | 59325 | 2-[[2-(acetyloxy)acetyl]-3,5-bis({[2,3-bis(acetyloxy)propyl]amino}carbonyl)-2,4,6-triiodoanilino]ethyl acetate | C30H36I3N3O15 | 详情 | 详情 |