US Patent 6,288,224
United States Patent and Trademark Office
Nycomed Salutar, Inc. (Wayne, PA) ; University of Iowa Research Foundation (Iowa City, IA, US)
Aziridines may be subjeted 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) ##STR1##where each R1 is independently hydrogen or a group AR and Ar is an optionally substituted phenyl group. The process comprises reacting a purified N-arylmethylethanolamine-sulphonate sulphonate ester with a base. N-aryimethyl-ethanolamine sulphonate ester of the formula R'NHCH2 CH2 OSO3 H, 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) ##STR2##where Ar and R1 are as hereinabove defined and at least two differing ArCHR21 moieties are present.
Vasilevskis, Janis; Varadarajan, John; Garrity, Martha; Fellmann, Jere Douglas; Messerle, Louis; and Amarasinghe, Gandara Preparation of n-arylmethyl aziridine derivatives, 1,4,7,10-tetraazacyclododecane derivatives obtained therefrom and n-arylethyl-ethanolamine sulphonate esters as intermediates. US Patent 6,288,224 filed April 10, 2000 and issued September 11, 2001. https://ir.uiowa.edu/patents/287