一种制备碘佛醇的方法

• Format: Patent
• Language: Chinese
• Published: 03.11.2023
• Subjects: ACYCLIC OR CARBOCYCLIC COMPOUNDS; CHEMISTRY; HETEROCYCLIC COMPOUNDS; METALLURGY; ORGANIC CHEMISTRY

本发明公开了一种药物碘佛醇的制备方法，属于医药中间体技术领域。从(5-羟基乙酰胺基)-N,N'-双(2,3-二羟丙基)-2,4,6-三碘-1,3-苯二甲酰胺(1)出发，经过丙酮叉保护得到中间体(2)；接着中间体(2)与氯乙醇发生取代反应得到中间体(3)，最后中间体(3)脱丙酮叉保护反应得到碘佛醇。本发明通过不同层级的保护，即使强碱性条件也不产生重排异构体，避免了杂质II的生成，工艺重现性好，可顺利放大到公斤级反应规模。 The invention discloses a preparation method of a medicine namely ioversol, and belongs to the technical field of medical intermediates. The preparation method comprises the following steps: carrying out acetonylidene protection on (5-hydroxyacetamido)-N,N'-bis(2,3-dihydroxypropyl)-2,4,6-triiodine-1,3-benzene dicarboxamide (1) to obtain an intermediate (2), carrying out substitution reaction on the intermediate (2) and chlorohydrin to obtain an intermediate (3), and finally, carrying out acetonylidene removal protection reaction on the intermediate (3) to obtain ioversol. Through protection of different levels, no rearrangement isomer is generated even under a strong alkaline condition, the generation of an impurity II is avoided, the process reproducibility is good, and the method can be smoothly amp