Dicyclohexylcarbodiimide → N,N'-Dicyclohexylurea

A solution of the gadolinium complex of 10-(2-hydroxy-3-(4-carboxyphenoxy)-propyl)- 1,4,7-tris(carboxymethyl)- 1,4,7,1 0-tetraazacyclododecane (500 mg, 0.72 mmol) in pyridine/formamide (1:1, 10 mL) was cooled to 0° C. with stirring. Dicyclohexylcarbodiimide (DCC, 149 mg, 0.72 mmol) and N,N-dimethylaminopyridine (DMAP, 20 mg, 0.16 mmol) were added. The resulting solution was stirred for 30 min at 0° C. A solution of dextran (MW 40,000; 1.0 g, 0.025 mmol) in formamide/pyridine (1:1, 30 mL) was prepared by gently warrning a suspension of the polysaccharide. The dextran solution was added to the activated chelate and the mixture was stirred at 25° C. for 4 days. During this time a precipitate of dicyclohexylurea formed. The suspension was filtered and the polysaccharide was precipitated by dropwise addition of the filtrate into ethanol/ether (1:2, 300 mL). The suspension was stirred for 30 min then allowed to settle. The solvent was decanted off and the solid was isolated by filtration. The product was purified by GPC on a column of Sephadex G-25 eluted with distilled H2O. Fractions corresponding to the macromolecular component were collected, pooled and lyophilized. To ensure there were no small molecular components unremoved by GPC an analytical sample was prepared by ultrafiltration (Centrex MWCO 10,000) of an aqueous solution (500 μL) containing the product (300 mg). The retentate was collected and lyophilized giving a white pad (296 mg). The UV spectrum of an aqueous solution of this product (0.175 mg/mL) had an absorbance at 258 nm which confirmed the presence of the benzoic acid ester. The analytical sample contained 0.92% gadolinium, corresponding to approximately 3 mol Gd/mol dextran.

1. stirringThe resulting solution was stirred for 30 min at 0° C
2. stirringthe mixture was stirred at 25° C. for 4 days

ORD record

ord-27fda6626f754b318378ac72879aba3c

Source dataset

uspto-grants-2001_11

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06312664B1