(5-氨基-2,4,6-三碘-1,3-亚苯基)二(羰基亚氨基-2,1,3-丙烷三基)四乙酸酯 | 148051-08-5

• 物质功能分类: 有机原料 - 羧酸类化合物及衍生物
• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 中文名称: (5-氨基-2,4,6-三碘-1,3-亚苯基)二(羰基亚氨基-2,1,3-丙烷三基)四乙酸酯
• 中文别名: N，N'-双[2-(乙酰氧基)-1-[[(乙酰氧基)甲基]乙基]-5-氨基-2,4,6-三碘-1,3-苯二甲酰胺
• 英文名称: N,N'-bis<2-(acetyloxy)-1-<(acetyloxy)methyl>ethyl>-5-amino-2,4,6-triiodo-1,3-benzenedicarboxamide
• 英文别名: ((5-amino-2,4,6-triiodoisophthaloyl)bis(azanyl))bis(propane-2,1,3-tril) tetraacetate；N,N'-bis[2-(acetyloxy)-1-[(acetyloxy)methyl]ethyl]-5-amino-2,4,6-triiodo-1,3-benzenedicarboxamide；N,N'-bis[2-(acetyloxy)l[(acetyloxy)-methyl]ethyl]-5-amino-2,4,6-triiodo-1,3-benzenedicarboxamide；[3-acetyloxy-2-[[3-amino-5-(1,3-diacetyloxypropan-2-ylcarbamoyl)-2,4,6-triiodobenzoyl]amino]propyl] acetate
• CAS: 148051-08-5
• 化学式: C₂₂H₂₆I₃N₃O₁₀
• 分子量: 873.176
• InChiKey: GUUCJQVOLIWIFP-UHFFFAOYSA-N

物化性质

• 沸点：
  723.6±60.0 °C(Predicted)
• 密度：
  1.934±0.06 g/cm3(Predicted)
• 溶解度：
  溶于氯仿

计算性质

• 辛醇/水分配系数(LogP)：
  1.4
• 重原子数：
  38
• 可旋转键数：
  16
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.45
• 拓扑面积：
  189
• 氢给体数：
  3
• 氢受体数：
  11

反应信息

• 作为反应物：
  描述：

  (5-氨基-2,4,6-三碘-1,3-亚苯基)二(羰基亚氨基-2,1,3-丙烷三基)四乙酸酯 在 N-碘代丁二酰亚胺 作用下， 以 氯仿 、 N,N-二甲基乙酰胺 、 溶剂黄146 为溶剂， 反应 21.5h， 生成 N,N'-Bis<2-(acetyloxy)-1-<(acetyloxy)methyl>ethyl>-5-<<5-<(acetyloxy)methyl>dihydro-2(3H)-furanylidene>amino>-2,4,6-triiodo-1,3-benzenedicarboxamide
  参考文献：
  名称：

  Heterocyclic Nonionic X-ray Contrast Agents. 4. The Synthesis of Dihydro-2(3H)-furanylidenamino, 5-oxo-1-pyrrolidinyl, and 5-oxo-4-morpholinyl Derivatives by an Intramolecular Iodocyclization Approach

  摘要：

  Intramolecular iodocyclization of omega-alkenylanilides 6 and [omega-(alkenyloxy)alkyl]anilides 7 resulted in the formation of dihydro-2(3H)-furanylidenamines 8 and 1,4-dioxan-2-ylideneamines 9, respectively, by an amide-oxygen participative nucleophilic attack on the expected iodonium intermediate. The latter heterocyclic ring system is new. If a strong base is present, the mode of ring closure was mainly diverted to an amide-nitrogen participative nucleophilic attack, leading to (iodomethyl)-pyrrolidinones 10 and (iodomethyl)morpholinones 11, from 6 and 7, respectively. Unique interconvertible syn-anti isomerism in the imino-ether 8a was demonstrated by variable temperature NMR studies. The major component in this mixture was the 8a anti-isomer. Acetolysis of the iodocyclized products, followed by deacetylation, provided the heterocyclically substituted polyhydroxytriiodoisophthalamides 16-18. Hydrolytic studies on the imidate 16d revealed an interesting pH dependence. As expected the amine 3d and the amide 22 resulted in pH values of 2 and 6. At pH 12, however, the Chapman rearrangement product 17d was the major product. The compounds obtained in this investigation are of interest as X-ray contrast agents.

  DOI：

  10.1021/jo00119a020
• 作为产物：
  描述：

  5-氨基间苯二甲酸 在 吡啶 、 氯化亚砜 、 potassium dichloroiodate 作用下， 以 N,N-二甲基乙酰胺 、 水 为溶剂， 反应 40.0h， 生成 (5-氨基-2,4,6-三碘-1,3-亚苯基)二(羰基亚氨基-2,1,3-丙烷三基)四乙酸酯
  参考文献：
  名称：

  Heterocyclic Nonionic X-ray Contrast Agents. III. The Synthesis of 5-[4-(Hydroxymethyl)-2-oxo-3-oxazolidinyl]-2,4,6-triiodo-1,3-benzenedicarboxamide Derivatives

  摘要：

  The syntheses of 2,4,6-triiodo-1,3-benzenedicarboxamide analogs, 12c, 12e, and 17c, of interest as X-ray diagnostic agents and in which the 5 position is linked to the N atom of a 4-(hydroxymethyl)-oxazolidin-2-one moiety, are described. The heterocycle was built from suitably protected 5-amino-2, 4,6-triiodo-1,3-benzenedicarboxylic acid derivatives by a three-step procedure consisting of (1) phosgene treatment to obtain the corresponding isocyanates, (2) phenylmercuric chloride-catalyzed addition of glycidol (10) resulting in glycidyl carbamates, and (3) pyridine-catalyzed intramolecular N-alkylation, followed by deprotection, to obtain the oxazolidin-2-ones. The intramolecular N-alkylation reaction was highly regioselective and was not appreciably accompanied by O-alkylation products under the experimental conditions employed. The two carboxamide nitrogen atoms in the intermediates and end products carry either 2,3-dihydroxypropyl or 1,3-dihydroxypropyl residues. These highly congested benzenoid compounds exhibited interesting NMR spectral features due to atropisomerism arising from hindrance to free rotation about the three single bonds that link the aromatic moiety to the N-containing functionalities.

  DOI：

  10.1021/jo00085a023

文献信息

• Nonionic radiographic contrast agents
  申请人：Bracco International B.V.

  公开号：US05614638A1

  公开（公告）日：1997-03-25

  New nonionic radiographic contrast agents having the formula ##STR1## wherein Y is a single bond, --CH.sub.2 CH.sub.2 --, --CH.sub.2 O--, --OCH.sub.2 --, ##STR2## --CH.sub.2 --, --CH.sub.2 --CH.sub.2 --CH.sub.2 --, --O-- or ##STR3## R.sub.1, R.sub.1 ' and R.sub.2 are the same or different and are hydrogen, alkyl or hydroxyalkyl. Hydroxyalkyl refers to such alkyl groups having 1 or more hydroxy groups. Preferred hydroxyalkyl groups include: ##STR4## R.sub.3 and R.sub.4 are the same or different and are hydrogen, methyl or --CH.sub.2 CH.sub.2 OH; R.sub.5 is hydrogen, alkyl, --CH.sub.2 CH.sub.2 OH, CH.sub.2 OH or OH and R.sub.6 is alkyl, --CH.sub.2 CH.sub.2 OH, CH.sub.2 OH, OH or hydrogen and may be the same or different than R.sub.5 and m is zero or one, with the proviso that no methylene or methine carbon atom of the heterocyclic ring is attached to both a nitrogen and an oxygen atom with the additional proviso that when Y is a single bond, m is not zero. These new contrast agents are water soluble and have desirable low osmolality and anticoagulant properties.

  新的非离子X线造影剂具有以下结构式：##STR1## 其中Y是单键，--CH.sub.2 CH.sub.2 --，--CH.sub.2 O--，--OCH.sub.2 --，##STR2## --CH.sub.2 --，--CH.sub.2 --CH.sub.2 --CH.sub.2 --，--O--或##STR3## R.sub.1，R.sub.1'和R.sub.2相同或不同，可以是氢，烷基或羟基烷基。羟基烷基指的是具有1个或更多羟基的烷基基团。首选的羟基烷基基团包括：##STR4## R.sub.3和R.sub.4相同或不同，可以是氢，甲基或--CH.sub.2 CH.sub.2 OH；R.sub.5是氢，烷基，--CH.sub.2 CH.sub.2 OH，CH.sub.2 OH或OH，R.sub.6是烷基，--CH.sub.2 CH.sub.2 OH，CH.sub.2 OH，OH或氢，可能与R.sub.5不同，m为零或一，但条件是杂环环的亚甲基或亚甲烷碳原子不同时连接到氮和氧原子，另外条件是当Y是单键时，m不为零。这些新的造影剂可溶于水，具有理想的低渗透压和抗凝血性能。
• PROCESS FOR THE PREPARATION OF IOPAMIDOL
  申请人：——

  公开号：US20010056206A1

  公开（公告）日：2001-12-27

  The present invention discloses a process for the preparation of pure non-ionic contrast agents. The invention also includes a method for purifying the non-ionic contrast agents.

  本发明公开了一种制备纯非离子造影剂的方法。该发明还包括一种纯化非离子造影剂的方法。
• Heterocyclic nonionic X-ray contrast agents V: A facile conversion of 2-tetrahydrofuroamides into α-hydroxy-δ-valerolactams and a general synthesis of lactams conjugated to 2,4,6-triiodoisophthalamides
  作者：E.R. Marinelli、T. Arunachalam、G. Diamantidis、J. Emswiler、H. Fan、R. Neubeck、K.M.R. Pillai、T.R. Wagler、C.-K. Chen、K. Natalie、N. Soundararajan、R.S. Ranganathan

  DOI：10.1016/0040-4020(96)00668-0

  日期：1996.8

  The synthesis of 2,4,6-triiodoisophthalamides substituted by a lactam moiety is described. A tandem ring opening-ring closure methodology consisting of a regiospecific ether cleavage of the tetrahydrofuroanilide 14b, followed by lactamization to α-oxygenated anilides 15b or 16b, gave α-O-functionalized-δ-valerolactams 12b or 13b, respectively. This approach is also compatible with the presence of ester

  描述了被内酰胺​​部分取代的2,4,6-三碘间苯二甲酰胺的合成。串联开环开环方法由四氢呋喃苯胺14b的区域特异性醚裂解，然后内酰胺化为α-氧化的酸酐15b或16b组成，分别得到α-O-官能化的δ-戊内酰胺12b或13b。该方法也与三碘苯基部分上酯和羰基氯官能团的存在兼容。还实现了内酰胺34–39的一般合成。进一步的化学修饰导致了水溶性的未取代内酰胺（34d，35d，37d）和α-羟基内酰胺[ 42（d，e），13（d，e）作为X射线造影剂而感兴趣的是图43和43 ]。
• Process for the preparation of iopamidol and the new intermediated therein
  申请人：——

  公开号：US20040082812A1

  公开（公告）日：2004-04-29

  A process for the preparation of (S)-N,N′-bis[2-hydroxy-1-(hydroxymethyl)ethyl]-5-[(2-hydroxy-1-oxo-propyl)amino]-2,4,6-triiodo-1,3-benzendicarboxamide (iopamidol) starling from 5-amino-N,N′-bis[2-hydroxy-1-(hydroxymethyl)ethyl]-2,4,6-triiodo-1,3-benzenedicarboxamide (II) which process comprises a) reacting the compound of formula (II) with a suitable protecting agent, to give a compound of formula (III) wherein R is a group of formula A or B wherein R 1 is a hydrogen atom, a C 1 ÷C 4 straight or branched alkoxy group, R 2 is hydrogen, a C 1 ÷C 4 straight or branched alkoxy group and R 3 ?is a C 1 ÷C 4 straight or branched alkyl group, a trifuoromethyl or a trichloromethyl group; b) acylating the amino group in position 5 of the intermediate compound of formula (III), by reaction with a (S)-2-(acetyloxy)propanoyl chloride to give a compound of formula (IV) wherein R is as defined above; and c) removing all the acyl groups present in the compound of formula (IV) under basic conditions, with prior cleavage of the cyclic protections of the hydroxy groups in the carboxamido substituents under acidic conditions, when R is a group of formula A carboxamido hydroxy groups under acidic conditions. The invention also refers to the new intermediates of formula (III) and (IV) wherein —R is a group A.

  一种制备(S)-N,N′-双[2-羟基-1-(羟甲基)乙基]-5-[(2-羟基-1-氧代-丙基)氨基]-2,4,6-三碘-1,3-苯二甲酰胺（iopamidol）的过程，从5-氨基-N,N′-双[2-羟基-1-(羟甲基)乙基]-2,4,6-三碘-1,3-苯二甲酰胺（II）开始，该过程包括a）将式（II）的化合物与适当的保护剂反应，以给出式（III）的化合物，其中R是式A或B的基团，其中R1是氢原子，C1-C4直链或支链烷氧基，R2是氢，C1-C4直链或支链烷氧基，R3是C1-C4直链或支链烷基，三氟甲基或三氯甲基基团；b）通过与(S)-2-(乙酰氧)丙酰氯反应，酰化式（III）中位置5的氨基，以给出式（IV）的化合物，其中R如上所定义；和c）在碱性条件下去除化合物中存在的所有酰基，在酸性条件下先裂解羧酰胺取代基的羟基环保护，当R是式A羧酰胺基团时，在酸性条件下去除羟基环保护。该发明还涉及式（III）和（IV）的新中间体，其中-R是A基团。
• Methods and compositions for using non-ionic contrast agents to reduce
  申请人：Bracco International B.V.

  公开号：US05527926A1

  公开（公告）日：1996-06-18

  In accordance with the present invention a novel method and composition for using nonionic contrast media to reduce the risk of clot formation in a diagnostic procedure is disclosed. Novel compositions for such method are also disclosed. The present method comprises employing a triiodinated phenyl contrast agent having a heterocyclic group or a dimeric triiodinated phenyl contrast agent having one or more heterocyclic groups.

  根据本发明，公开了一种新的方法和组合物，用于使用非离子造影剂来减少诊断过程中凝血风险。还公开了用于此类方法的新型组合物。本方法包括使用具有杂环基团的三碘苯造影剂或具有一个或多个杂环基团的二聚三碘苯造影剂。