A new synthesis of rizatriptan based on radical cyclization

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 d...

Full description

Saved in:
Bibliographic Details
Published inCollection of Czechoslovak chemical communications Vol. 73; no. 1; pp. 116 - 126
Main Authors Radl, Stanislav, Klecan, Ondrej, Klvana, Robert, Havlicek, Jaroslav
Format Journal Article
LanguageEnglish
Published PRAGUE 6 Inst Organic Chem And Biochem 01.01.2008
Blackwell Publishing Ltd
Subjects
Chemical synthesis
Chemistry
Chemistry, Multidisciplinary
Migraine
Pharmaceuticals
Physical Sciences
Science & Technology
radical cyclizations
rizatriptan
HETEROCYCLES
serotonin agonists
Mannich reaction
5-HT1D RECEPTOR AGONIST
PALLADIUM-CATALYZED CYCLIZATION
5-SUBSTITUTED INDOLE-DERIVATIVES
triptans
Indoles
SUMATRIPTAN
migraine treatment drugs
Online AccessGet full text

Cover

More Information
Summary: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.
ISSN:0010-0765
1212-6950
2192-6506
DOI:10.1135/cccc20080116