SB-272183
5-氯-6-(4-甲基哌嗪-1-基)-N-[4-(4-吡啶)萘-1-基]吲哚哚-1-羧酰胺Chemical Name: 5-Chloro-6-(4-methylpiperazin-1-yl)-N-[4-(4-pyridyl)naphthalen-1-yl]indoline-1-carboxamide
CAS No. 216058-27-4
项目整合开发状态: Preclinical
项目研究机构: GlaxoSmithKline (Originator)
合成路线:Suzuki coupling of 4-bromonaphth-1-ylamine (I) with 4-pyridylboronic acid (II) furnished 4-(pyridyl)-1-naphthylamine (III),which was further converted into isocyanate (IV) by treatment with triphosgene.
合成路线:Catalytic hydrogenation of 1-acetyl-6-nitroindoline (V) afforded amine (VI).Condensation of (VI) with mechlorethamine hydrochloride (VIII) in the presence of K2CO3 in refluxing n-butanol produced piperazinylindoline (X).Alternatively,intermediate (X) was obtained by Sandmeyer reaction of amine (VI) in the presence of CuBr,followed by condensation of the resulting bromide (VII) with N-methylpiperazine (IX).Chlorination of (X) with N-chlorosuccinimide provided (XI).The acetamide function of (XI) was then hydrolyzed in refluxing 2M HCl to give amine (XII).Finally,coupling of (XII) with isocyanate (IV) gave rise to the corresponding urea.
📌 参考资料/链接：
参考文献标题:Indole derivs.having combined 5HT1A,5HT1B and 5HT1D receptor antagonist activity
文献作者:Gaster,L.M.; Rami,H.K.; Wyman,P.A.(SmithKline Beecham plc)
参考来源:EP 0975593; WO 9850358
📄 详细内容
合成路线:Suzuki coupling of 4-bromonaphth-1-ylamine (I) with 4-pyridylboronic acid (II) furnished 4-(pyridyl)-1-naphthylamine (III),which was further converted into isocyanate (IV) by treatment with triphosgene.
合成路线:Catalytic hydrogenation of 1-acetyl-6-nitroindoline (V) afforded amine (VI).Condensation of (VI) with mechlorethamine hydrochloride (VIII) in the presence of K2CO3 in refluxing n-butanol produced piperazinylindoline (X).Alternatively,intermediate (X) was obtained by Sandmeyer reaction of amine (VI) in the presence of CuBr,followed by condensation of the resulting bromide (VII) with N-methylpiperazine (IX).Chlorination of (X) with N-chlorosuccinimide provided (XI).The acetamide function of (XI) was then hydrolyzed in refluxing 2M HCl to give amine (XII).Finally,coupling of (XII) with isocyanate (IV) gave rise to the corresponding urea.
参考文献标题:Mixed 5-HT1A/1B/1D receptor antagonists as novel antidepressants
文献作者:Evans,M.; Gaster,L.M.; Gordon,l.; et al.
参考来源:16th Int Symp Med Chem (Sept 18 2000,Bologna) 2000,Abst PB-77
产品链接: CAS No. 216058-27-4››