Iomeprol, E-7337, B-16880, Imeron, Iomeron, -Drug Synthesis Database

【结构式】

【药物名称】Iomeprol, E-7337, B-16880, Imeron, Iomeron

【化学名称】N,N'-Bis(2,3-dihydroxypropyl)-2,4,6-triiodo-5-(N-methylglycolamido)isophthalamide
　　　　　　N,N'-Bis(2,3-dihydroxypropyl)-5-[(hydroxyacetyl)methylamino]-2,4,6-triiodo-1,3-benzenedicarboxamide

【CA登记号】78649-41-9

【分子式】C₁₇H₂₂I₃N₃O₈

【分子量】777.09339

【开发单位】Bracco (Originator), Altana Pharma (Licensee), Eisai (Licensee)

【药理作用】Contrast Mediums, Diagnostic Agents

合成路线1 合成路线2

合成路线1

Treatment of 5-amino-2,4,6-triiodo-1,3-benzenedicarboxylic acid (I) with thionyl chloride yields the dichloride (II). Compound (II) is treated with acetoxyacetyl chloride to give compound (III), which is methylated with iodomethane. Condensation with 3-amino-1,2-propanediol of the N-methyl derivative (IV) thus obtained, followed by deacetylation with alkali metal hydroxide, yields iomeprol.

参考文献中间体

【1】 Felder, E.; Musu, C.; Fumagalli, L.; Uggeri, F. (Bracco SpA); Preparation of 5-acylamino-2,4,6-triiodo- or tribromo-benzoic acid derivs.. WO 8809328 .
【2】 Davies, A.; Felder, E.; Tirone, P.; IOMEPROL < Rec INN; BAN; USAN >. Drugs Fut 1990, 15, 11, 1074.
【3】 Musu, C.; Felder, E.; Fumagalli, L.; Piva, R.; Uggeri, F.; Smiles rearrangement, a new synthetic pathway to the synthesis of 5-(hydroxyacyl)-amino-2,4,6-triiodoisophthalamides. Invest Radiol 1990, 25, Suppl. 1, S100-1.

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(B)	12979	3-Amino-1,2-propanediol；3-aminopropane-1,2-diol	616-30-8	C₃H₉NO₂	详情	详情
(A)	16601	ethyl chloroacetate; ethyl 2-chloroacetate	105-39-5	C₄H₇ClO₂	详情	详情
(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)	31195	2-[3,5-bis(chlorocarbonyl)-2,4,6-triiodoanilino]-2-oxoethyl acetate		C₁₂H₆Cl₂I₃NO₅	详情	详情
(IV)	31196	2-[3,5-bis(chlorocarbonyl)-2,4,6-triiodomethylanilino]-2-oxoethyl acetate		C₁₃H₈Cl₂I₃NO₅	详情	详情

合成路线2

5-Hydroxy-1,3-benzenedicarboxylic acid dimethyl ester (I) is treated with 3-amino-1,2-propanediol to give the corresponding bisamide (II), which is then iodinated with iodine monochloride. The reaction of the triiodinated compound thus obtained (III) with sodium methoxide and chloroacetic acid ethyl ester yields N,N'-bis(2,3-dihydroxypropyl)-2,4,6-triiodo-5-[2-ethoxy-2-oxoethoxy]-1,3-benzenedicarboxamide (IV), which is treated with methylamine to give the 5-[2-(methylamino)-2-oxoethoxy] derivative (V). Iomeprol is obtained through a Smiles-type intramolecular rearrangement of (V) in aqueous alkaline medium.

参考文献中间体

【1】 Felder, E.; Pitre, D. (Bracco SpA); Derivs. of 2,4,6-triiodo-isophthalic acid, processes for their synthesis and x-ray contrasting materials containing these. EP 0026281; US 4352788 .
【2】 Davies, A.; Felder, E.; Tirone, P.; IOMEPROL < Rec INN; BAN; USAN >. Drugs Fut 1990, 15, 11, 1074.

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(B)	12979	3-Amino-1,2-propanediol；3-aminopropane-1,2-diol	616-30-8	C₃H₉NO₂	详情	详情
(A)	16601	ethyl chloroacetate; ethyl 2-chloroacetate	105-39-5	C₄H₇ClO₂	详情	详情
(I)	31197	dimethyl 5-hydroxyisophthalate	13036-02-7	C₁₀H₁₀O₅	详情	详情
(II)	31198	N(1),N(3)-bis(2,3-dihydroxypropyl)-5-hydroxyisophthalamide		C₁₄H₂₀N₂O₇	详情	详情
(III)	31199	N(1),N(3)-bis(2,3-dihydroxypropyl)-5-hydroxy-2,4,6-triiodoisophthalamide		C₁₄H₁₇I₃N₂O₇	详情	详情
(IV)	31200	ethyl 2-(3,5-bis[[(2,3-dihydroxypropyl)amino]carbonyl]-2,4,6-triiodophenoxy)acetate		C₁₈H₂₃I₃N₂O₉	详情	详情
(V)	31201	N(1),N(3)-bis(2,3-dihydroxypropyl)-2,4,6-triiodo-5-[2-(methylamino)-2-oxoethoxy]isophthalamide		C₁₇H₂₂I₃N₃O₈	详情	详情

Extended Information