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    • 8. 发明公开
    • 5-[아세틸(2,3-디히드록시프로필)아미노]-N,N'-비스(2,3-디히드록시프로필)-2,4,6-트리요오도-1,3-벤젠디카르복스아미드의제조방법
    • 制备5-乙酰基(2,3-二羟基丙基)氨基-N,N'-二(2,3-二羟基丙基)-2,4,6-三羟甲基-1,3-苯二甲酰胺的方法
    • KR1020000029649A
    • 2000-05-25
    • KR1019997000722
    • 1998-05-19
    • 브라코 쏘시에떼 퍼 아찌오니
    • 데산티스,니콜라
    • C07C233/00
    • C07C227/18C07C231/02C07C231/08C07C237/52C07C233/33C07C229/62
    • PURPOSE: The present invention relates to a novel process for the preparation of 5-£acetyl(2,3-dihydroxypropyl)amino|-N,N'-bis(2,3-dihydroxypropyl)-2,4,6-triiodo-1,3-benzenedicarboxamide, more commonly known under the name iohexol, one of the most widely used non-ionic X-ray contrast agents, starting from the compound of, 5 - amino - 2,4,6 - triiodo - 1,3-benzenedicarboxylic acid. CONSTITUTION: The process for the preparation of 5 - £acetyl(2,3-dihydroxypropyl) amino| -N,N'-bis(2,3-dihydroxypropyl)-2,4,6-triiodo-1,3-benzenedicarboxamide of formula (I), starting from 5-amino-1,3-benzenedicarboxylic acid of formula (II), comprising the following steps: step a) is the reaction in heterogeneous phase between 5-amino-2,4,6-triiodo-1,3-benzenedicarboxylic acid and thionyl chloride in a solvent selected from the group consisting of: straight or branched (C7-C16) hydrocarbons, (C7-C8) aromatic hydrocarbons, 1,1,1-trichloroethane, n-butyl acetate, diglyme (diethylene glycol dimethyl ether), in the presence of catalytic amounts of a tertiary amine, to give compound (III); step b) is the acetylation reaction of compound (III) with glacial acetic acid both as the solvent and the reagent and thionyl chloride; step c) is the formation of compound (V) by reaction of the compound (IV) with 1-amino-2,3-propanediol, by reaction of compound (IV) in a dipolar aprotic solvent, selected from the group of dimethylformamide (DMF), dimethylacetamide (DMA), dimethylsulfoxide (DMSO) or N-methyl-pyrrolidinone; step d) is the alkylation of the compound (V) in aqueous solution at basic pH, by addition of a sodium hydroxide-calcium hydroxide mixture, with 3-chloro-1,2-propanediol or epichlorohydrin, at a temperature of 40-90°C.
    • 目的:本发明涉及一种制备5-乙酰基(2,3-二羟丙基)氨基| -N,N'-双(2,3-二羟丙基)-2,4,6-三碘 - 1,3-苯二甲酰胺,以俗名“碘海醇”为名,最常用的非离子X射线造影剂之一,以5-氨基-2,4,6-三碘代-1,3 - 苯二甲酸。 构成:制备5 - 乙酰基(2,3-二羟基丙基)氨基的方法 (I)的N,N'-双(2,3-二羟基丙基)-2,4,6-三碘-1,3-苯二甲酰胺,由式(II)的5-氨基-1,3-苯二羧酸 ),其包括以下步骤:步骤a)是在选自以下的溶剂中的5-氨基-2,4,6-三碘-1,3-苯二甲酸与亚硫酰氯之间的非均相中的反应:直链或 (C7-C16)烃,(C7-C8)芳族烃,1,1,1-三氯乙烷,乙酸正丁酯,二甘醇二甲醚(二甘醇二甲醚)在催化量的叔胺存在下反应,得到 化合物(III); 步骤b)是化合物(III)与冰乙酸作为溶剂和试剂和亚硫酰氯的乙酰化反应; 步骤c)是通过化合物(IV)与1-氨基-2,3-丙二醇的反应,通过化合物(IV)在偶极非质子溶剂中的反应形成化合物(V),所述偶极非质子溶剂选自二甲基甲酰胺 DMF),二甲基乙酰胺(DMA),二甲基亚砜(DMSO)或N-甲基 - 吡咯烷酮; 步骤d)是在碱性pH下,通过在40-90℃的温度下加入氢氧化钠 - 氢氧化钙混合物与3-氯-1,2-丙二醇或表氯醇将化合物(Ⅴ)烷基化 C。