An efficient Fischer Indole synthesis of Avitriptan, a potent 5-HT1D receptor agonist

PR Brodfuehrer, BC Chen, TR Sattelberg…

Index: Brodfuehrer; Chen; Sattelberg T.R.; Smith; Reddy; Stark; Quinlan; Reid Journal of Organic Chemistry, 1997 , vol. 62, # 26 p. 9192 - 9202

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Citation Number: 51

Abstract

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 hydrazine 6 and 5-chlorovaleraldehyde, 20, to give the chloropropylindole 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 ...