公开(公告)号：EP2489655A1

公开(公告)日：2012-08-22

申请号：EP10823275.2

申请日：2010-09-22

申请人： The University of Tokushima

发明人： NEMOTO, Hisao ,  KAWAMURA, Tomoyuki ,  YATSUZUKA, Kenji ,  KAMIYA, Masaki

IPC分类号： C07C227/16 ,  C07C229/30 ,  C07C233/47 ,  C07C271/08 ,  C07C271/12 ,  C07D207/452

CPC分类号： C07D207/452 ,  C07C227/16 ,  C07C233/47 ,  C07C271/08 ,  C07C271/12 ,  C07C229/30

摘要： The objective of the present invention is to provide a process for simple and efficient preparation of an intermediate compound to synthesize a gadolinium complex having a substituent for improving a retention property in blood time and specificity to an intended organ. The objective of the present invention is also to provide an intermediate compound produced by the said production process. The process for preparation of the diethylenetriaminepentaacetic acid derivative (I):

wherein R 1 to R 5 are independently C 1-6 alkyl groups;
comprising the steps of:
reacting a diethylenetriaminepentaacetic acid pentaester with a halogenated ally compound in an aprotic solvent;
removing the excess halogenated ally compound (III); and
reacting a reaction product of the diethylenetriaminepentaacetic acid pentaester and the halogenated ally compound with a base in a solvent.

摘要翻译： 本发明的目的是提供简单有效地制备中间体化合物以合成具有取代基的钆络合物的方法，以提高对血液时间的保留性和对预期器官的特异性。 本发明的目的还在于提供通过所述制备方法制备的中间体化合物。 制备二亚乙基三胺五乙酸衍生物（I）的方法：其中R 1至R 5独立地为C 1-6烷基; 包括以下步骤：使二亚乙基三胺五乙酸五酯与卤素化合物在非质子溶剂中反应; 除去过量的卤代烯化合物（III）; 并将二亚乙基三胺五乙酸五酯与卤代烯化合物的反应产物与碱在溶剂中反应。