201798-91-6Relevant academic research and scientific papers
An efficient Fischer indole synthesis of avitriptan, a potent 5-HT(1D) receptor agonist
Brodfuehrer,Chen,Sattelberg T.R.,Smith,Reddy,Stark,Quinlan,Reid
, p. 9192 - 9202 (2007/10/03)
An efficient synthesis of antimigraine drug candidate avitriptan (1, BMS 180048) is reported. The key step is a two-phase Fischer indolization reaction between hydrazine 6 and 5-chlorovaler-aldehyde, 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 compound in 40-45% overall yield. Significant improvements in the syntheses of the known starting materials, hydrazine 6, 5- chlorovaleraldehyde, 20, and 4-chloro-5-methoxypyrimidine, 24, were also achieved.
