Process for the preparation of macrocyclic chelants and the chel

Drug – bio-affecting and body treating compositions – In vivo diagnosis or in vivo testing – Magnetic imaging agent

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540465, 540474, A61B 5055, C07D48722

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active

060428104

ABSTRACT:
A process for the preparation of complexes of macrocyclic chelants with paramagnetic metal trivalent ions of formula (XII) ##STR1## wherein R.sub.1, R.sub.2 and Me.sup.3+ are as described in the following, comprising: a) reaction of 1,4,7,10-tetraazacyclododecane with triethyl orthoformate to give 5H,9bH-2a,4a,7,9a-octahydrotetraazacycloocta[cd]pentalene; b) carboxymethylation reaction in water; c) hydrolysis reaction in basic conditions; d) alkylation according to known methods with an epoxide in water; e) complexation according to known methods carried out in water by addition of a paramagnetic metal salt; f) purification by diafiltration, final desalting of the aqueous solution on ion exchange resins and g) crystallization or recovery.

REFERENCES:
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patent: 5277895 (1994-01-01), Platzek et al.
patent: 5447635 (1995-09-01), Viscardi et al.
patent: 5747000 (1998-05-01), Platzek et al.
patent: 5925752 (1999-07-01), Ripa et al.
Dischino et al Inorg. Chem. 1991, 30, pp 1265-9 Synthesis of Gadolinium (+)-10-(1-Hydroxypropan-2-yl)-1,4,7,10-tetraazacyclododecane-1,4,7-triyltr iacetate etc.
Weisman et al Tetrahedron Letters vol. 21, 1980 pp 3635-8.

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