- 【药物名称】Aminoglutethimide, AG-1, Orimeten, Cytadren
- 【化学名】3-(4-Aminophenyl)-3-ethyl-2,6-piperidinedione
- 【CAS登记号】125-84-8
- 【结构式】
- 【分子式】C13-H16-N2-O2
- 【分子量】232.2814
- 【原研厂家】Novartis (Originator)
- 【作用类别】Adrenocortical Dysfunction Therapy, Breast Cancer Therapy, Cushing's Syndrome, Agents for, ENDOCRINE DRUGS, Oncolytic Drugs, Prostate Cancer Therapy, Antiglucocorticoids, Aromatase Inhibitors
- 【研发状态】Launched-1981
- 【合成情况】
- 〖来源〗Org Process Res Dev
- 〖合成路线〗
- 〖标题〗Production of (R)-aminogluthimide: A new route from 1-chloro-4-nitrobenzene
- 〖合成方法〗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.
- 〖作者〗Bunegar, M.J.; et al.
- 〖参考〗Bunegar, M.J.; et al.; Production of (R)-aminogluthimide: A new route from 1-chloro-4-nitrobenzene. Org Process Res Dev 1999, 3, 6, 442
- 〖出处〗Org Process Res Dev1999,3,(6):442
- 〖备注〗
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