(4,7,10-Tris-carboxymethyl-1,4,7,10-tetraaza-cyclododec-1-yl)-acetic acid; hydrochloride

• 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
• 英文名称: (4,7,10-Tris-carboxymethyl-1,4,7,10-tetraaza-cyclododec-1-yl)-acetic acid; hydrochloride
• 英文别名: 2-[4,7,10-Tris(carboxymethyl)-1,4,7,10-tetrazacyclododec-1-yl]acetic acid;hydrochloride；2-[4,7,10-tris(carboxymethyl)-1,4,7,10-tetrazacyclododec-1-yl]acetic acid;hydrochloride
• 化学式: C₁₆H₂₈N₄O₈*2ClH
• 分子量: 477.342
• InChiKey: IFDLKQIKJCOWCX-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -2.03
• 重原子数：
  29
• 可旋转键数：
  8
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.75
• 拓扑面积：
  162
• 氢给体数：
  5
• 氢受体数：
  12

反应信息

• 作为反应物：
  描述：

  (4,7,10-Tris-carboxymethyl-1,4,7,10-tetraaza-cyclododec-1-yl)-acetic acid; hydrochloride 在 calcium hydroxide 、 sodium hydroxide 作用下， 以 水 为溶剂， 生成 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid dicalcium
  参考文献：
  名称：

  {Ca(OH2)3[Ca(DOTA)].7.7H2O}n

  摘要：

  The octadentate ligand H(4)DOTA (H(4)DOTA = 1,4,7,10-tetraazacyclododecane-N,N',N '',N triple prime-tetraacetic acid) forms the most stable calcium complexes known. The overall solid-state structure of the title complex {poly[triaqua-mu-(1,4,7,10-tetraazacyclododecane- N,N',N '',N triple prime-tetraacetato)-dicalcium 7.7-hydrate], [Ca-2(C16H24N4O8)(H2O)(3)].7.7H(2)O} contains two independent eight-coordinate Ca2+ ions on a twofold crystallographic axis with the Ca2+ ions bound to four of the eight O atoms [mean Ca-O = 2.45 (3) Angstrom] and the four N atoms [mean Ca-N = 2.59 (2) Angstrom] of the DOTA ligand. The coordination geometry of the Ca atom encapsulated by the DOTA ligand is distorted square antiprismatic. Carboxylate bridges link [Ca(DOTA)](2-) anions to [Ca(OH2)(3)](2+) counterions (on general positions related by the twofold symmetry) to form a neutral tetranuclear unit, which in turn bridges to surrounding units through a carboxylate O atom and generates a one-dimensional chain.

  DOI：

  10.1107/s0108270195013916
• 作为产物：
  描述：

  氯乙酸 、 轮环藤宁 在 盐酸 、 氢氧化钾 作用下， 生成 (4,7,10-Tris-carboxymethyl-1,4,7,10-tetraaza-cyclododec-1-yl)-acetic acid; hydrochloride
  参考文献：
  名称：

  多元氮杂环烷烃-N-essigsäuren

  摘要：

  合成了一系列的聚氮杂环烷-N-乙酸，它们的环大小在12-18个成员之间变化，并且在烷基中具有取代基，并且根据供体原子的构象研究了它们的络合特性。

  DOI：

  10.1016/s0040-4020(01)97695-1

文献信息

• METHOD FOR PREPARING 1,4,7,10-TETRAAZACYCLODODECANE-1,4,7,10-TETRAACETIC ACID
  申请人：VIWIT PHARMACETICAL CO., LTD.

  公开号：US20200347023A1

  公开（公告）日：2020-11-05

  Disclosed is a method for preparing 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) of formula (II), comprising the following steps: carrying out an alkylation reaction on cyclen in formula (I) and XCH 2 COOR in the presence of an acid-binding agent in water; adjusting a pH value to separate out a crude product of DOTA; and recrystallizing. The preparation method of the present invention is applicable to large-scale industrial production of DOTA, the whole process does not need to adopt an ion-exchange resin or low-temperature refrigeration mode for purification, and the purity and yield of the product are higher.

  本发明公开了一种制备1,4,7,10-四氮杂环十二烷-1,4,7,10-四乙酸（DOTA）的方法，包括以下步骤：在水中存在酸中和剂的情况下对公式（I）中的环烷进行烷基化反应，以及XCH2COOR；调节pH值分离出DOTA的粗品；并进行重结晶。本发明的制备方法适用于大规模工业生产DOTA，整个过程不需要采用离子交换树脂或低温冷却模式进行纯化，产品的纯度和收率更高。
• PROCESS FOR THE PURIFICATION OF POLYAMINOCARBOXYLATES
  申请人：Biophore India Pharmaceuticals Pvt. Ltd.

  公开号：US20140323719A1

  公开（公告）日：2014-10-30

  The present invention relates to an improved process for the purification of polyaminocarboxylates such as DOTA, DTPA, DO3A-butrol, BOPTA.

  本发明涉及一种改进的聚氨基羧酸盐（如DOTA、DTPA、DO3A-butrol、BOPTA）的纯化过程。
• [EN] PROCESS FOR PURIFYING 1,4,7,10-TETRAAZACYCLODODECANE-1,4,7,10-TETRAACETIC ACID<br/>[FR] PROCÉDÉ DE PURIFICATION D'ACIDE 1,4,7,10-TÉTRAAZACYCLODODÉCANE-1,4,7,10-TÉTRAACÉTIQUE
  申请人：AGFA HEALTHCARE

  公开号：WO2015117911A1

  公开（公告）日：2015-08-13

  A process for purifying a compound of formula (1), comprising the following steps: a) adding an acid to an aqueous solution of the compound of formula 1, including salts thereof so as to obtain a pH ≤ 3 whereby a slurry is obtained; and b) filtering the slurry and at least one time washing the obtained precipitate with a liquid comprising water; and c) dissolving the precipitate obtained in step b) in water to obtain an aqueous solution; and d) filtering of the solution obtained in step c) over a nanofiltration membrane having a Molecular Weight Cut Off in the range from 150 to 500 and wherein optionally, between step c) and step d) the pH of the aqueous solution is adjusted to a pH value in the pH range as specified by the manufacturer of the nanofiltration membrane. A process for preparing a gadolinium complex of the purified compound of formula 1 is also disclosed. This gadolinium complex can be used for making a pharmaceutical composition as a contrast agent for magnetic resonance imaging.

  一种用于纯化式（1）化合物的方法，包括以下步骤：a）向式1化合物的水溶液中添加酸，包括其盐，以获得pH≤3，从而得到悬浊液；b）过滤悬浊液，并至少用一种含水的液体洗涤所得到的沉淀物；c）将步骤b）中得到的沉淀物溶解在水中，以获得水溶液；并d）将步骤c）中得到的溶液通过分子量截止在150至500范围内的纳滤膜过滤，其中在步骤c）和步骤d）之间，可以选择性地将水溶液的pH调整为纳滤膜制造商指定的pH范围内的pH值。还公开了制备纯化式1化合物的钆配合物的方法。该钆配合物可用作磁共振成像的造影剂制备制药组合物。
• [EN] PROCESS FOR PRODUCING 1, 4, 7, 10-TETRAAZACYCLODODECANE-1, 4, 7, 10-TETRAACETIC ACID AND COMPLEXES THEREOF<br/>[FR] PROCÉDÉ DE PRODUCTION D'ACIDE 1,4,7,10-TÉTRAAZACYCLODODÉCANE-1,4,7,10-TÉTRAACÉTIQUE ET DE COMPLEXES DE CELUI-CI
  申请人：AGFA HEALTHCARE

  公开号：WO2014114664A1

  公开（公告）日：2014-07-31

  The present invention relates to a process for producing 1, 4, 7, 10-tetraazacyclododecane-1, 4, 7, 10-tetraacetic acid (DOTA) including salts and hydrates thereof of general formula (I) from the respective cyclen. Said process further involves the use of cationic- and anionic exchange resins and solvent treatments to remove the organic and inorganic contaminants. Any cations present in the raw DOTA or other contaminants resulting from the reaction of cyclen are largely reduced in early stages of the process allowing to obtain good yields of DOTA in a purified grade and in an easier and reliable way. The present invention is thus useful for the production of DOTA, of macrocyclic compounds comprising metal ions complexes thereof and of compositions comprising said macrocyclic compounds that can be used as contrast agents for magnetic resonance imaging.

  本发明涉及一种生产1,4,7,10-四氮杂环十二烷-1,4,7,10-四乙酸（DOTA）及其盐和水合物的方法，其通式为（I），该方法进一步涉及使用阳离子和阴离子交换树脂和溶剂处理以去除有机和无机污染物。在该过程的早期阶段，原始的DOTA中存在的任何阳离子或由cyclen反应产生的其他污染物都被大大减少，从而使得可以更容易地、可靠地获得高纯度的DOTA，并获得良好的收率。因此，本发明对于生产DOTA、包括其金属离子配合物的大环化合物以及包括该大环化合物的组合物，可用作磁共振成像对比剂，具有实用价值。
• PROCESS FOR PRODUCING 1,4,7,10-TETRAAZACYCLODODECANE-1,4,7,10-TETRAACETIC ACID AND COMPLEXES THEREOF
  申请人：AGFA HEALTHCARE

  公开号：US20160024030A1

  公开（公告）日：2016-01-28

  A process for producing 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) including salts and hydrates thereof of general formula (I) from the respective cyclen. The process involves the use of cationic- and anionic exchange resins and solvent treatments to remove the organic and inorganic contaminants. Any cations present in the raw DOTA or other contaminants resulting from the reaction of cyclen are largely reduced in early stages of the process allowing to obtain good yields of DOTA in a purified grade and in an easier and reliable way. The process is useful for the production of DOTA, of macrocyclic compounds including metal ions complexes thereof and of compositions including the macrocyclic compounds that can be used as contrast agents for magnetic resonance imaging.

  一种从相应的环状化合物制备1,4,7,10-四氮杂环十二烷-1,4,7,10-四乙酸（DOTA）及其盐和水合物（I式）的方法，该方法涉及使用阳离子和阴离子交换树脂和溶剂处理以去除有机和无机污染物。在该过程的早期阶段，原始DOTA中存在的任何阳离子或由环状化合物反应产生的其他污染物都大大减少，从而可以更容易、更可靠地获得高纯度的DOTA产量。该过程对于生产DOTA、包括金属离子配合物的大环化合物以及包括大环化合物的组成物，可用作磁共振成像的对比剂，具有实用价值。