药物详细合成路线
| Name | Aminoglutethimide;AG-1;Orimeten;Cytadren | | Chemical Name | 3-(4-Aminophenyl)-3-ethyl-2,6-piperidinedione | | CAS | 125-84-8 | | Related CAS | | | Formula | C13H16N2O2 | | Structure |  | | Formula Weight | 232.28467 | | Stage | 上市-1981 | | Company | Novartis (Originator) | | Activity/Mechanism | Adrenocortical Dysfunction Therapy, Breast Cancer Therapy, Cushings Syndrome, Agents for, ENDOCRINE DRUGS, Oncolytic Drugs, Prostate Cancer Therapy, Antiglucocorticoids, Aromatase Inhibitors | | Syn. Route | 1 | | Route 1 | | 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. | | |  | | List of intermediates | No. | | (4s,7r,8s,9s,16s)-8-hydroxy-5,5,7,9,13-pentamethyl-16-[(e)-1-methyl-2-(2-methyl-1,3-thiazol-4-yl)ethenyl]-4-[(triethylsilyl)oxy]oxa-13-cyclohexadecene-2,6-dione | (i) | | 1-methyl-2-oxo-1,2-dihydro-4-pyridinecarbaldehyde | | | 2-(2-phenyl-1h-indol-3-yl)-1-ethanamine; 2-(2-phenyl-1h-indol-3-yl)ethylamine | | | (1as,8r,9as)-3-(acetoxy)-7-(benzyloxy)-5-[[(benzyloxy)methoxy]methyl]-8-(hydroxymethyl)-1-[(4-methylphenyl)sulfonyl]-1,1a,2,3,8,9a-hexahydro-9h-azireno[2,3-c][1]benzazocin-9-one | (ii) | | (1as,8r,9as)-7-(benzyloxy)-5-[[(benzyloxy)methoxy]methyl]-3-hydroxy-8-(hydroxymethyl)-1-[(4-methylphenyl)sulfonyl]-1,1a,2,3,8,9a-hexahydro-9h-azireno[2,3-c][1]benzazocin-9-one | (iii) | | (8r,9s,10s,12s)-6-(benzyloxy)-4-[[(benzyloxy)methoxy]methyl]-8-(hydroxymethyl)-11-[(4-methylphenyl)sulfonyl]-14-oxa-1,11-diazatetracyclo[7.4.1.0(2,7).0(10,12)]tetradeca-2,4,6-trien-9-ol | (iv) | | (1s,6r,15s,17s)-8-(benzyloxy)-10-[[(benzyloxy)methoxy]methyl]-16-[(4-methylphenyl)sulfonyl]-2,4,18-trioxa-13,16-diazapentacyclo[11.4.1.0(1,6).0(7,12).0(15,17)]octadeca-7,9,11-trien-3-one | (v) | | [(8r,9s,10s,12s)-6-(benzyloxy)-4-[[(benzyloxy)methoxy]methyl]-9-hydroxy-11-[(4-methylphenyl)sulfonyl]-14-oxa-1,11-diazatetracyclo[7.4.1.0(2,7).0(10,12)]tetradeca-2,4,6-trien-8-yl]methyl carbamate | (vi) | | (8r,10s,12s)-8-[[(aminocarbonyl)oxy]methyl]-6-(benzyloxy)-4-[[(benzyloxy)methoxy]methyl]-11-[(4-methylphenyl)sulfonyl]-14-oxa-1,11-diazatetracyclo[7.4.1.0(2,7).0(10,12)]tetradeca-2,4,6-trien-9-yl acetate | (vii) | | (8r,10s,12s)-8-[[(aminocarbonyl)oxy]methyl]-6-(benzyloxy)-4-[[(benzyloxy)methoxy]methyl]-14-oxa-1,11-diazatetracyclo[7.4.1.0(2,7).0(10,12)]tetradeca-2,4,6-trien-9-yl acetate | (viii) | | | Reference 1: 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. |
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来源:药化网
作者:药化小编
摘要:本文合成路线介绍的是药物中文名氨鲁米特；英文名Aminoglutethimide;AG-1;Orimeten;Cytadren；CAS[125-84-8]
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