An efficient Fischer indole synthesis of avitriptan, a potent 5-HT1D receptor agonist

被引:52
作者
Brodfuehrer, PR
Chen, BC
Sattelberg, TR
Smith, PR
Reddy, JP
Stark, DR
Quinlan, SL
Reid, JG
机构
[1] Bristol Myers Squibb Co, Tech Operat Div, Proc Explorat Labs 1, Syracuse, NY 13221 USA
[2] Bristol Myers Squibb, Pharmaceut Res Inst, Chem Proc Res, New Brunswick, NJ 08903 USA
关键词
D O I
10.1021/jo971368q
中图分类号
O62 [有机化学];
学科分类号
070303 ; 081704 ;
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 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 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.
引用
收藏
页码:9192 / 9202
页数:11
相关论文
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