Aminoglutethimide, AG-1, Orimeten, Cytadren

氨鲁米特Chemical Name: 3-(4-Aminophenyl)-3-ethyl-2,6-piperidinedione
CAS No. 125-84-8
项目整合开发状态: Launched-1981
项目研究机构: Novartis (Originator)
合成路线:An improved procedure for the large-scale preparation of (R)-aminoglutethimide has been reported.Nucleophilic substitution of 1-chloro-4-nitrobenzene (I) with methyl cyanoacetate afforded the (nitrophenyl)cyanoacetate (II),which was alkylated with diethyl sulfate in the presence of Et3N,yielding (III).Hydrolysis and decarboxylation of the cyano ester (III) by means of K2CO3 in aqueous MeOH provided the arylbutyronitrile (IV).Subsequent Michael addition with methyl acrylate gave adduct (V).This was hydrolyzed to the cyano acid (VI),which was further resolved with (-)-cinchonidine,yielding the desired (R)-enantiomer (VII).Acid-catalyzed cyclization of (VII) in boiling toluene generated the glutarimide derivative (VIII).The nitro group of (VIII) was finally reduced to the title amino derivative by hydrogenation over Pd/C.