LY-334370
4-氟-N-(3-(1-甲基哌啶-4-基)-1H-吲哚-5-基)苯甲酰胺盐酸盐 4-氟-N-[3-(1-甲基-4-哌啶基)-1H-吲哚-5-基]苯甲酰胺盐酸盐Chemical Name: 4-Fluoro-N-[3-(1-methylpiperidin-4-yl)-1H-indol-5-yl]benzamide fumarate
CAS No. 182563-09-3, 182563-08-2 (free base), 199673-74-0 (monoHCl)
项目整合开发状态: Phase II
项目研究机构: Lilly (Originator), Synaptic (Originator)
合成路线:Condensation of 5-nitroindole (I) with 1-methyl-4-piperidone (II) in the presence of KOH produced tetrahydropyridinyl indole (III).Subsequent catalytic hydrogenation of (III) over Pd/C gave the 5-amino-3-piperidinylindole (VI).In a related procedure,5-aminoindole (IV) was condensed with piperidone (II),and the resulting tetrahydropyridine (V) was hydrogenated to yield (VI).Aminoindole (VI) was finally condensed with 4-fluorobenzoyl chloride (VII) to produce the corresponding amide,which was isolated as the fumarate salt.
📌 参考资料/链接：
参考文献标题:5-Substd.-3-(1,2,3,6-tetrahydropyridin-4-yl)- and 3-(piperidin-4-yl)-1H-indoles: New 5-HT1F agonists
文献作者:Audia,J.E.; Dressman,B.A.; Droste,J.J.; Fritz,J.E.; Kaldor,S.W.; Koch,D.J.; Krushinski,J.H.Jr.; Nissen,J.S.; Rocco,V.P.; Schaus,J.M.; Thompson,D.C.(Eli Lilly and Company)
参考来源:EP 0733628; JP 1999502816; US 5708008; WO 9629075
📄 详细内容
合成路线:Condensation of 5-nitroindole (I) with 1-methyl-4-piperidone (II) in the presence of KOH produced tetrahydropyridinyl indole (III).Subsequent catalytic hydrogenation of (III) over Pd/C gave the 5-amino-3-piperidinylindole (VI).In a related procedure,5-aminoindole (IV) was condensed with piperidone (II),and the resulting tetrahydropyridine (V) was hydrogenated to yield (VI).Aminoindole (VI) was finally condensed with 4-fluorobenzoyl chloride (VII) to produce the corresponding amide,which was isolated as the fumarate salt.
合成路线:Acylation of 4-nitroaniline (I) with 4-fluorobenzoyl chloride (II) affords benzanilide (III).Catalytic hydrogenation of the nitro group of (III) employing Pt/C then gives amine (IV).Diazotization of (IV),followed by reduction with SnCl2 leads to hydrazine (V).Reaction of 5-chloro-2-pentanone (VI) with dimethylamine yields the amino ketone (VII).Finally,the title compound is obtained by Fisher indole synthesis from aryl hydrazine (V) and ketone (VII) under acidic conditions.
参考文献标题:Use of a serotonin 5-HT1F agonist in the manufacture of a medicament for treating or ameliorating the symptoms of common cold or allergic rhinitis
文献作者:Johnson,K.W.; Phebus,L.A.(Eli Lilly and Company)
参考来源:EP 0824917; US 5962473; WO 9806402
合成路线:Condensation of 5-nitroindole (I) with 1-methyl-4-piperidone (II) in the presence of KOH produced tetrahydropyridinyl indole (III).Subsequent catalytic hydrogenation of (III) over Pd/C gave the 5-amino-3-piperidinylindole (VI).In a related procedure,5-aminoindole (IV) was condensed with piperidone (II),and the resulting tetrahydropyridine (V) was hydrogenated to yield (VI).Aminoindole (VI) was finally condensed with 4-fluorobenzoyl chloride (VII) to produce the corresponding amide,which was isolated as the fumarate salt.
参考文献标题:A method for the prevention of migraine
文献作者:Johnson,K.W.; Phebus,L.A.(Eli Lilly and Company)
参考来源:WO 9811895
产品链接: CAS No.182563-08-2›› 产品链接: CAS No.199673-74-0››