公开(公告)号：WO9628420A3

公开(公告)日：1996-12-12

申请号：PCT/GB9600552

申请日：1996-03-08

Applicant: NYCOMED SALUTAR INC ,  UNIV IOWA RES FOUND ,  COCKBAIN JULIAN ,  MESSERLE LOUIS ,  AMARASINGHE GANDARA ,  FELLMANN JERE DOUGLAS ,  GARRITY MARTHA ,  VARADARAJAN JOHN ,  VASILEVSKIS JANIS

Inventor： MESSERLE LOUIS ,  AMARASINGHE GANDARA ,  FELLMANN JERE DOUGLAS ,  GARRITY MARTHA ,  VARADARAJAN JOHN ,  VASILEVSKIS JANIS

IPC: A61K49/00 ,  A61K49/06 ,  C07C303/44 ,  C07C305/06 ,  C07D203/08 ,  C07D255/00 ,  C07D257/02 ,  C07D259/00 ,  C07C305/04

CPC classification number: C07D203/08 ,  A61K49/0002 ,  A61K49/06 ,  C07C303/44 ,  C07D255/00 ,  C07D257/02 ,  C07D259/00 ,  C07C305/06

Abstract: Aziridines may be subjected to a cyclooligomerization reaction to produce polyazacycloalkane compounds useful for example in the preparation of chelating agents for use in diagnostic imaging contrast agents. N-benzyl-aziridine in particular is useful as it can be cyclotetramerized and debenzylated to yield cyclen, a key intermediate in chelating agent preparation. The invention provides a particularly attractive route to production of N-benzyl and other N-arylmethyl aziridines of formula (I), (where each R1 independently is hydrogen or a group Ar and Ar is an optionally substituted phenyl group), said process comprising reacting a purified N-arylmethylethanolamine-sulphonate ester with a base. N-arylmethyl-ethanolamine sulphonate ester of the formula: R'NHCH2CH2OSO3H, wherein the N-arylmethyl group R' is an N-(bisarylmethyl) or N-(triarylmethyl) group, as intermediates. In a further aspect the invention provides compounds of formula (II), where Ar and R1 are as hereinbefore defined and at least two differing ArCHR1 moieties are present.

Abstract translation: 氮杂环丁烷可以被喷射到环烯化反应中以产生用于例如制备用于诊断成像造影剂的螯合剂的多氮杂环烷烃化合物。 特别是N-苄基 - 氮丙啶是有用的，因为它可以进行环化聚合和脱苄基化，以产生螯合剂，螯合剂制备中的关键中间体。 本发明提供了生产式（I）的N-苄基和其它N-芳基甲基氮丙啶的特别有吸引力的途径，其中每个R 1独立地为氢或基团AR，Ar为任选取代的苯基。 该方法包括使纯化的N-芳基甲基乙醇胺 - 磺酸酯磺酸酯与碱反应。 作为中间体，式R'NHCH2CH2OSO3H的N-芳基甲基 - 乙醇胺磺酸酯，其中N-芳基甲基R'是N-（二芳基甲基）或N-（三芳基甲基）基团。 在另一方面，本发明提供式（II）的化合物，其中Ar和R 1如上所定义，并且存在至少两个不同的ArCHR 21部分。

公开(公告)号：WO1996028420A2

公开(公告)日：1996-09-19

申请号：PCT/GB1996000552

申请日：1996-03-08

Applicant: NYCOMED SALUTAR, INC. ,  UNIVERSITY OF IOWA RESEARCH FOUNDATION ,  COCKBAIN, Julian ,  MESSERLE, Louis ,  AMARASINGHE, Gandara ,  FELLMANN, Jere, Douglas ,  GARRITY, Martha ,  VARADARAJAN, John ,  VASILEVSKIS, Janis

Inventor： NYCOMED SALUTAR, INC. ,  UNIVERSITY OF IOWA RESEARCH FOUNDATION ,  COCKBAIN, Julian

IPC: C07D203/08

CPC classification number: C07D203/08 ,  A61K49/0002 ,  A61K49/06 ,  C07C303/44 ,  C07D255/00 ,  C07D257/02 ,  C07D259/00 ,  C07C305/06

Abstract: Aziridines may be subjected to a cyclooligomerization reaction to produce polyazacycloalkane compounds useful for example in the preparation of chelating agents for use in diagnostic imaging contrast agents. N-benzyl-aziridine in particular is useful as it can be cyclotetramerized and debenzylated to yield cyclen, a key intermediate in chelating agent preparation. The invention provides a particularly attractive route to production of N-benzyl and other N-arylmethyl aziridines of formula (I), (where each R1 independently is hydrogen or a group Ar and Ar is an optionally substituted phenyl group), said process comprising reacting a purified N-arylmethylethanolamine-sulphonate ester with a base. N-arylmethyl-ethanolamine sulphonate ester of the formula: R'NHCH2CH2OSO3H, wherein the N-arylmethyl group R' is an N-(bisarylmethyl) or N-(triarylmethyl) group, as intermediates. In a further aspect the invention provides compounds of formula (II), where Ar and R1 are as hereinbefore defined and at least two differing ArCHR1 moieties are present.

Abstract translation: 氮丙啶可以进行环烯基化反应以产生用于例如制备用于诊断成像造影剂的螯合剂的多氮杂环烷烃化合物。 特别是N-苄基 - 氮丙啶是有用的，因为它可以进行环化聚合和脱苄基化，以产生螯合剂，螯合剂制备中的关键中间体。 本发明提供了生产式（I）的N-苄基和其它N-芳基甲基氮丙啶的特别有吸引力的途径（其中每个R 1独立地为氢或基团Ar，Ar为任选取代的苯基），所述方法包括使 纯化的N-芳基甲基乙醇胺 - 磺酸酯与碱。 具有下式的N-芳基甲基 - 乙醇胺磺酸酯：R'NHCH2CH2OSO3H，其中N-芳基甲基R'为N-（二芳基甲基）或N-（三芳基甲基）基团，为中间体。 在另一方面，本发明提供式（II）化合物，其中Ar和R 1如上所定义，并且存在至少两个不同的ArCHR 1部分。