The Synthetic Study Of Naratriptan

Naratriptan, an important drug belong to the second generation Triptans for the treatment of acute attracts of migraine, exhibited high affinity for 5-HT1B/1D receptor. It was developed by GlaxoSmithKline Co., and first marketed in England in 1997. The pathogenesis of migraine, the acting mechanism and development of anti-migraine drugs were briefly described in this thesis. The acting mechanism, the pharmacokinetics, the therapeutic effect and the side effects about naratriptan were also described in this thesis.Here disclosed a new synthesis of naratriptan via the employing the new protecting group that could avoid the complicate indole synthesis and therefore shorten the synthetic route. Hence, starting from indoline, Naratriptan was synthesized via an 9-step sequence such as Vilsmeier-Haauc Reaction, aromatization, C-C coupling reaction, catalytic hydrogenation and N-debenzylation in 23.8% overall yield. The structure of the target molecule was determined by 1H NMR and ESI-MS.In the case of the last step related to the deprotection of benzyl group, it was extensively studied about the methodology such as the ratio of the reaction materials loaded, the type and amount of the catalysts, reaction temperature, and solvents, and finally found that Birch reduction with sodium in liquid ammonia at low temperature was nice for the N-debenzylation of compound 48.