藥物詳細合成路線
| Name | Nabilone;LY-109514;Cesamet | | Chemical Name | (±)-trans-6,6-Dimethyl-3-(1,1-dimethylheptyl)-1-hydroxy-6,6a,7,8,10,10a-hexahydro-9H-dibenzo[b,d]pyran-9-one | | CAS | 51022-71-0 | | Related CAS | | | Formula | C24H36O3 | | Structure |  | | Formula Weight | 372.55272 | | Stage | 上市-1983 | | Company | Lilly (Originator), Valeant (Licensee) | | Activity/Mechanism | Nausea and Vomiting, Treatment of, NEUROLOGIC DRUGS, Cannabinoid Receptor Agonists | | Syn. Route | 1 | | Route 1 | | the condensation of diethyl 2-acetylglutarate (i) with 5-(1,1-dimethylheptyl)resorcinol (ii) by means of pocl3 gives ethyl 7-(1,1-dimethylheptyl)-5-hydroxy-4-methyl-2-oxo-2h-1-benzopyran-3-propionate (iii), which is cyclized by means of nah in dmso yielding 3-(1,1-dimethylheptyl)-7,10-dihydro-1-hydroxy-6h-dibenzo[b,d]pyran-6,9-(8h)-dione (iv). the ketalization of (iv) with ethylene glycol (a) and p-toluenesulfonic acid affords the ketal (v), which by a grignard reaction with methylmagnesium iodide in refluxing ether is converted into dl-3-(1,1-dimethylheptyl)-6,6a,7,8-tetrahydro-1-hydroxy-6,6-dimethyl-9h-dibenzo[b,d]pyran-9-one (vi). finally, this compound is reduced with li in liquid ammonia. | | |  | | List of intermediates | No. | | (1r,4as,10ar)-7-isopropyl-1,4a-dimethyl-6-sulfo-1,2,3,4,4a,9,10,10a-octahydro-1-phenanthrenecarboxylic acid | (a) | | ethyl 3-[3-(benzyloxy)-2-pyridinyl]propanoate | (i) | | 5-(2-chlorophenyl)-7-nitro-1,3-dihydro-2h-1,4-benzodiazepine-2-thione | (vii) | | 1,4-dimethyl-10-methoxy-2,3,4,5,6,7-hexahydro-1,6-methano-1h-4-benzazonine-7(6h)-one; (1r,9r)-4-methoxy-1,11-dimethyl-11-azatricyclo[7.4.1.0(2,7)]tetradeca-2,4,6-trien-8-one | (ii) | | 2-formylphenylboronic acid | (iii) | | ethyl 2-formyl[1,1-biphenyl]-3-carboxylate | (iv) | | ethyl 2-[(hydroxyimino)methyl][1,1-biphenyl]-3-carboxylate | (v) | | ethyl 2-(aminomethyl)[1,1-biphenyl]-3-carboxylate | (vi) | | | Reference 1: archer, r.a.; hexahydro-dibenzo[b,d]pyran-9-ones as analgesic drugs. us 3944673 . Reference 2: archer, r.a.; dihydroxyhexahydrodibenzo[b,d]pyrans. de 2451934; es 431674; fr 2249664; gb 1487637; jp 50071678; us 3968125 . Reference 3: archer, r.a.; hexahydro-dibenzo[b,d]pyran-9-ones as an anti-anxiety drug. de 2451932; es 431675; fr 2249663; gb 1487636; jp 50082073; nl 7414437; us 3928598 . Reference 4: archer, r.a.; hexahydro-dibenzo[b,d]pyran-9-ones as psychotropic, particularly anti-depressant drugs. us 3953603 . Reference 5: castaner, j.; weetman, d.f.; nabilone. drugs fut 1978, 3, 3, 207. |
|
來源:藥化網
作者:藥化小編
摘要:本文合成路線介紹的是藥物中文名納比隆；英文名Nabilone;LY-109514;Cesamet；CAS[51022-71-0]
|
