An efficient fischer indole synthesis of avitriptan, a potent 5-HT_1D receptor agonist

摘要

An efficient synthesis of the antimigraine drug candidate avitriptan (1.BMS 180048) is reported. The key step is a two-phase Fischer indolization reaction between hydrazing 6 and 5-chlorovaler- Aldehyde, 20 to give the chloroproylindole 35, which is susceptible to acid-catalyzed degradation Under the reaction conditions required for its formation. Sequential coupling of 35 with piperazine, 26, and 4-chloro-5-methoxypyrimidine, 24, gives the title compound in 40-45/100 overall yield.