首先以异喹啉为原料, 经氧化生成氮氧化物后与苯甲酰氯和水作用, 得到1-羟基异喹啉, 收率为73.3%. 以Fasudil 为原料, 经氨基保护、氧化, 在相转移催化剂的存在下, 于二氯甲烷和水的两相体系中与苯甲酰氯和水作用, 合成羟基Fasudil, HPLC 纯度大于99%, 总收率为46.8%, 从而建立了一条条件温和、操作简便的羟基Fasudil 的合成工艺路线.
1-Isoquinolinol was synthesized from isoquinoline via oxidation, reaction with benzoyl chloride and water in yield of 73.3%. According to this process, a method for the synthesis of hydroxyfasudil [1-(1-hydroxy-5-isoquinolinesulfonyl)- homopiperazine] from fasudil [hexahydro-1-(5-isoquinoline-sulfonyl)-1H-1,4-diazepine] was estabilshed in this paper. The process undergoes effectively through protection for amino, oxidation, reaction with water in a water/dichloromethane biphase system in the presence of phase transfer catalyst and benzoyl chloride and then deprotection. The objective product was finally obtained in yield of 46.8% with a purity more than 99% (HPLC). It is virtually a practical process with mild reaction conditions and simple operation.
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