Background: The 3-Substituted indoles are found to possess a wide range of biological and
pharmacological activities. The efficient and impurity free scalable preparation of 2-(1H-Indol-5-yl)-
ethanesulfonic acid methylamide has been successfully achieved for the synthesis of Naratriptan and
its novel 3-substituted derivatives.
Method: The preparation of 2-(1H-Indol-5-yl)-ethanesulfonic acid methylamide involves the condensation
of (2,2-Dimethoxy-ethyl)-trimethylammonium bromide with thiophenol followed by Fischer indolisation
with polyphosphoric acid. Finally, desulfurisation was achieved using catalytic amount of
Raney nickel under hydrogen pressure to target the synthetic precursor in good yield.
Results: The synthesis of Naratriptan has been explored from the 2-(1H-Indol-5-yl)-ethanesulfonic
acid methylamide obtained under modified reaction condition. Some novel 3-substituted indole derivatives
were also synthesized from the same synthetic precursor. Structures of all the new compounds
were confirmed by the spectral data (IR, 1H-NMR, 13C-NMR and Mass).
Conclusion: A significantly improved and commercially viable method has been developed for the
preparation of the synthetic precursor for Naratriptan and its novel 3-substituted derivatives. This
method furnished impurity free target products in good to excellent yield.