Process, useful e.g. to prepare isolated 5-(N-2,3-dihydroxypropylacetamido)-2,4,6-triiodo-N-(2,3-dihydroxyethyl)-isophthalamide compound as active principle for non-ionic X-ray imaging, comprises atomization of an ioxilan aqueous solution

摘要

#CMT# #/CMT# Process for preparing an isolated 5-(N-2,3-dihydroxypropylacetamido)-2,4,6-triiodo-N-(2,3dihydroxyethyl)-isophtalamide compound (ioxilan) (I) comprises atomization of an ioxilan aqueous solution. #CMT# : #/CMT# Independent claims are included for: (1) a isolated ioxilan product obtained by the process and it has an instant solubility of at least 500 mg of iodine/mg and at a temperature of lower than 40[deg]C; and (2) a sterile injectable solution comprising (I) having 300-500 mg of iodine/ml, preferably 350-450 mg of iodine/ml. #CMT#USE : #/CMT# The process is useful for the preparation of (I) and sterile injectable solution (claimed), where (I) is useful as an active principle for the non-ionic X-ray imaging. #CMT#ADVANTAGE : #/CMT# The isolated ioxilan product has an instant solubility of at least 500 mg of iodine/mg. The process is carried out without crystallization step (all claimed) hence the process is simple and cost effective. #CMT#ORGANIC CHEMISTRY : #/CMT# Preferred Components: The temperature in the atomization unit outlet is less than 130[deg]C, preferably 100-110[deg]C. The ioxilan aqueous solution is ensued from the manufacture of the ioxilan without crystallization step. #CMT#EXAMPLE : #/CMT# 5-(N-2,3-Diacetoxypropylacetamido)-2,4,6-triiodo-N-(2,3-acetoxy-ethyl)-N'-(2,3-dihydroxypropyl)-isophtalamide compound (45.85 g) in methanol (100 ml) was added to 1M sodium methylate in methanol (10.5 ml). The solution was shaken for 30 minutes to obtain complete deprotection of the solution, at the same time methyl acetate was removed by distillation under vacuum of its azeotrope with methanol. The solution was neutralized to pH 7 with Dowex 50 H+ (RTM: Crosslinking cationic exchange resin) and diluted with water (75 ml). Methanol was removed by distillation under vacuum to obtain 5-(N-2,3-dihydroxypropylacetamido)-2,4,6-triiodo-N-(2,3-dihydroxypropyl)-N'-(2-hydroxyethyl)-isophtalamide compound (yield 85% and purity of 98.5-99.5%).