8-氟-3,4-二氢异喹啉的合成及其转化为 1,8-二取代四氢异喹啉。

Directorate of Drug Substance Development, Egis Pharmaceuticals Plc., P.O. Box 100, H-1475 Budapest, Hungary.

Molecules. 2018 May 26;23(6):1280. doi: 10.3390/molecules23061280.

A simple procedure for the synthesis of 8-fluoro-3,4-dihydroisoquinoline is described below, based on a directed -lithiation reaction. This key intermediate was then applied in various transformations. Fluorine⁻amine exchange afforded the corresponding 8-amino-3,4-dihydroisoquinolines, suitable starting compounds for the synthesis of 1-substituted 8-amino-tetrahydroisoquinolines. On the other hand, reduction and alkylation reactions of 8-fluoro-3,4-dihydroisoquinoline led to novel 1,2,3,4-tetrahydroisoquinoline derivatives that can be used as building blocks in the synthesis of potential central nervous system drug candidates.

下面描述了一种基于导向锂化反应的合成 8-氟-3,4-二氢异喹啉的简单方法。该关键中间体随后应用于各种转化。氟⁻胺交换得到相应的 8-氨基-3,4-二氢异喹啉，它们是合成 1-取代的 8-氨基四氢异喹啉的合适起始化合物。另一方面，8-氟-3,4-二氢异喹啉的还原和烷基化反应导致了新型的 1,2,3,4-四氢异喹啉衍生物，它们可用作潜在中枢神经系统药物候选物合成中的构建块。