非离子型X-射线造影剂碘普罗胺的合成

Synthesis of the non-ionic X-ray contrast medium iopromide

目的:研究和改进非离子型X-射线造影剂碘普罗胺的合成工艺。方法:以5-氨基-2,4,6-三碘异酞酰氯、甲氧基乙酸和三光气为原料,经酰氯化、酰胺化和再酰胺化制得重要中间体3-[(2-甲氧基)乙酰胺基]-5-(2,3-二羟基-N-甲基丙胺基甲酰基)-2,4,6-三碘苯甲酰氯(4)。4再与2,3-二羟基丙胺经酰胺化制得碘普罗胺。结果:中间体及目标化合物经质谱、核磁共振谱、红外光谱等确证,整个工艺的总收率为76.3%。结论:本路线杂质易控、成本较低、条件温和、步骤少,适合工业化生产。

Objective： To investigate and improve the synthesis of the non-ionic X-ray contrast medium iopromide. Methods： The important intermediate 3-（ 2-methoxyacetylamino）-5-（ 2,3-dihydroxy N-methylpropylcarbamoyl）-2,4,6-triiodobenzoyl chloride（ 4） was prepared from 2,4,6-triiodosophthalic dichloride,methoxyactic acid,and bis（ trichloromethyl） carbonate by chlorination,amidation and amidination. Iopromide was synthesized from 4 and 2,3-dihydroxypropylamine by amidation. Results： The structure of intermediates and target compound was identified by MS and1H-NMR. The overall yield was 76. 3%. Conclusion： This improved method can be used industrially with simple and easily controlling by-product,a lower cost,mild condition and fewer reaction steps.