Recent Advances in the Synthesis of Naratriptan: An Anti-Migraine Drug

Naratriptan 1 is a selective serotonin 5-hydroxytryptamine 5-HT1 receptor subtype agonist used for the treatment of acute attacks of migraine headaches and for cluster headaches. Since its discovery in 1998 by GlaxoSmithKline, a number of synthetic methods have been reported up till now. This review aims to focus soberly the various synthetic key routes used for the synthesis of naratriptan 1 in high yields. An effort has been carried out to provide an overview of practical, safe and scalable methods for the preparation of naratriptan, describing various Pd-catalyzed Heck reactions, Matsuda– Heck coupling, Fischer indolizations, Sonogashira coupling, Japp-Klingemann reaction and TiCl4- mediated indolization. Moreover, the precursors utilized in the synthesis have been described briefly.