Abstract

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.

Keywords: Indole, triptan, pharmacologically, desulfurisation, Fischer indolisation, synthetic.

Graphical Abstract