Donitriptan hydrochloride, F-11356
4-(4-(2-(3-(2-氨基乙基)-1H-吲哚-5-基氧基)乙酰基)哌嗪-1-基)苯甲腈盐酸盐 4-(4-(2-(3-(2-氨基乙基)-1H-吲哚-5-基氧基)乙酰基)哌嗪-1-基)苯甲腈 Chemical Name: 4-[4-[2-[3-(2-Aminoethyl)-1H-indol-5-yloxy]acetyl]piperazin-1-yl]benzonitrile hydrochloride
CAS No. 170911-68-9, 170912-52-4 (free base), 200615-15-2 (monomethanesufonate salt)
项目整合开发状态: Phase II
项目研究机构: Pierre Fabre (Originator)
合成路线:The protection of the 3-(2-aminoethyl)-1H-indol-5-ol (I) with di-tert-butyl dicarbonate gives the corresponding carbamate (II),which is condensed with the chloroacetyl piperazine (III) (obtained by reaction of 4-(1-piperazinyl) benzonitrile (IV) with chloroacetyl chloride (V) by means of CaCO3) using K2CO3 and KI in refluxing 2-butanone to yield the protected target compound (V).Finally,this compound is deprotected with TFA in toluene.
📌 参考资料/链接：
参考文献标题:Indole-derived azylpiperazines as ligands for 5HT1-like receptors 5HT1B and 5HT1D
文献作者:Halazy,S.; Perez,M.; Briley,M.; Pauwels,P.(Pierre Fabre M閐icament)
参考来源:EP 0729455; FR 2712591; JP 1997505072; US 5726177; WO 9514004
📄 详细内容
合成路线:The condensation of 2-[3-(2-aminoethyl)-1H-indol-5-yloxy]acetic acid (I) with 4-(1-piperazinyl)benzonitrile (II) by means of ethyl chloroformate in dichloromethane gives the protected target compound (III),which is finally deprotected with methanesulfonic acid in dichloromethane.
参考文献标题:Methanesulphonate salt of an arylpiperazine derived from tryptamine and its solvates for pharmaceutical use
文献作者:Halazy,S.; Perez,M.(Pierre Fabre M閐icament)
参考来源:EP 0923549; WO 9748680
合成路线:F-11356 is easily synthesized from serotonin following two synthetic pathways.The first method involves the preparation of 2-[3-[2-[N-(tert-butoxycarbonyl)amino]ethyl]-1H-indol-5-yloxy]acetic acid,which is obtained by protection of serotonin with BOC2O/NaOH,followed by O-alkylation with methyl bromoacetate and saponification of the methyl ester with KOH.The overall yield for the three steps was 81%.A coupling reaction between this acid and a phenyl piperazine derivative afforded the N-BOC-protected desired products which,upon subsequent treatment with trifluoroacetic anhydride,gave the free amines.In the second method,the phenylpiperazine derivatives were first treated with chloroacetylchloride and then the intermediates were allowed to react with N-BOC-serotonin to give the N-BOC-protected desired products.At this stage,and before the final deprotection,the R group can be modified to afford other analogues.
参考文献标题:F-11356
文献作者:Perez,M.; John,G.W.; Colpaert,F.C.; Pauwels,P.J.; Halazy,S.
参考来源:Drugs Fut 1999,24(6),605