盐酸多奈哌齐杂质的合成

Synthesis of the Impurity of Donepezil Hydrochloride

为控制盐酸多奈哌齐的药品质量,建立盐酸多奈哌齐原料药的质量标准,从多奈哌齐的合成路线入手,分析并合成其中可能存在的2个杂质2-[(1-苄基-4-哌啶基)甲基]-5-羟基-6-甲氧基-2,3-二氢-1-茚酮和2-[(1-苄基-4-哌啶基)甲基]-5-甲氧基-6-羟基-2,3-二氢-1-茚酮,并经1H-NMR和MS确证结构。这些杂质可作为盐酸多奈哌齐原料药质量控制中的杂质对照品,从而对杂质进行准确地定量、定性分析。

To strengthen the quality control over donepezil hydrochloride and establish its quality criterion, two impurities of donepezil hydrochloride were identified based on the synthetic route and synthesized, and their structures wereconfirmed by 1H-NMR and MS. These substances were 2-（（1-benzylpiperidin-4-yl）methyl）-2,3-dihydro-5-hydroxy-6-methoxyinden-1-one and 2-（（l-benzylpiperidin-4-yl）methyl）-2,3-dihydro-6-hydroxy-5-methoxyinden-l-one. These impurities could be used as donepezil hydrochloride impurity reference substance of quality control, thus accurate quantitative and qualitative analysis of impurities.