目的对组胺H3受体拮抗剂/反向激动剂pitolisant进行合成工艺研究。方法以对氯氯苄、丙二酸二乙酯为起始原料,经过缩合、水解、脱羧、还原、酯化、取代反应制得pitolisant。结果与结论经过6步反应合成目标化合物pitolisant,其结构经1H-NMR及MS确证。对其中多步反应条件进行了工艺考察及优化,总收率为31.4%(以对氯氯苄计)。 OBJECTIVE To synthesize the histamine H3 receptor antagonist / inverse agonist pitolisant. Methods Starting from p-chlorobenzyl chloride and diethyl malonate, the solution of pitolisant was prepared by condensation, hydrolysis, decarboxylation, reduction, esterification and substitution reactions. Results and Conclusion The target compound, pitolisant, was synthesized through 6 steps. Its structure was confirmed by 1H-NMR and MS. The multi-step reaction conditions were investigated and optimized. The total yield was 31.4% (based on p-chlorobenzyl chloride).