Collect. Czech. Chem. Commun. 2008, 73, 116-126

A New Synthesis of Rizatriptan Based on Radical Cyclization

Stanislav Rádl*, Ondřej Klecán, Robert Klvaňa and Jaroslav Havlíček

Zentiva, U kabelovny 130, 102 37 Prague 10, Czech Republic


A new methodology useful for preparation of indole derivatives bearing a 2-(dialkylamino)-ethyl substituent at the 3-position has been developed. Application of this methodology to the synthesis of N,N-dimethyl-2-{5-[(1H-1,2,4-triazol-1-yl)methyl]-1H-indol-3-yl}ethan-1-amine (rizatriptan; 3) is described. The key reaction step is based on the radical cyclization of N-[4-(dimethylamino)but-2-yn-1-yl]-N-{2-iodo-4-[(1H-1,2,4-triazol-1-yl)methyl]phenyl}-acetamide (21), easily available by the Mannich reaction, and subsequent isomerization of the primarily formed methylidene derivative 22.

Keywords: Rizatriptan; Triptans; Migraine treatment drugs; Serotonin agonists; Radical cyclizations; Indoles; Mannich reaction.

References: 26 live references.