甲磺酸沙芬酰胺的合成工艺改进

Improved synthesis of safinamide mesylate

目的合成抗帕金森药甲磺酸沙芬酰胺并优化其合成工艺。方法以间氟氯苄和对羟基苯甲醛为起始原料,经醚化、醛胺缩合、还原、成盐、纯化得到目标化合物甲磺酸沙芬酰胺。结果与结论目标化合物的结构经1H-NMR、MS谱确证。改进后的工艺操作简单,总收率达到60.36%(以间氟氯苄的摩尔质量计),产物纯度达到99.90%,该合成路线适合工业化生产。

Safinamide mesylate, an anti-Parkinson drug, was developed by Newron Company. Safinamide operates by several mechanisms, including inhibition of the uptake of monoamine oxidase-B （MAO-B） and dopamine, sodium and calcium channel modulation, and reduction of glutamate release in the central nervous system. In this paper, a new synthetic route has been established based on the literatures. Using 3-fluoro- benzyl chloride and p-hydroxybenzaldehyde as the starting material, safinamide mesylate was synthesized through four steps, including substitution, condensation, reduction, salification and purification. The total yield of safinamide mesylate is 60. 36% （based on the molar mass of 3-fluorobenzyl chloride）and its purity is 99.90 %. Its structure was confirmed by 1H-NMR, MS spectra. The improved process has several advantages over these reported procedures, such as mild conditions and simple operations. Anyway it＇s more suitable for industrial production.