LY-349950

Chemical Name: N-[3-[2-(Dimethylamino)ethyl]-2-methyl-1H-indol-5-yl]-4-fluorobenzamide hydrochloride
CAS No. 189805-93-4, 189806-34-6 (free base)
项目整合开发状态: Preclinical
项目研究机构: Lilly (Originator), Synaptic (Originator)
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.
📌 参考资料/链接:
参考文献标题:N-[2-Substd.-3-(2-aminoethyl)-1H-indol-5-yl]-amides: New 5-HT1F agonists
文献作者:Fritz,J.E.; Hahn,P.J.; Kaldor,S.W.; Siegel,M.G.; Xu,Y.-C.(Eli Lilly and Company)
参考来源:EP 0768301; JP 1999513666; WO 9713512

📄 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: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:N-[3-(2-Dimethylaminoethyl)-2-methyl-1-H-indol-5-yl]-4-fluorobenzamide: A potent,selective,and orally active 5-HT1F receptor agonist potentially useful for migraine therapy
文献作者:Xu,Y.-C.; Johnson,K.W.; Phebus,L.A.; Cohen,M.L.; Nelson,D.L.; Schenck,K.; Walker,C.D.; Fritz,J.E.; Kaldor,S.W.; LeTourneau,M.E.; Murff,R.E.; Zgombick,J.M.; Calligaro,D.O.; Audia,J.E.; Schaus,J.M.
参考来源:J Med Chem 2001,44(24),4031


产品链接: CAS No.189806-34-6››