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��；英文名Nabilone;LY-109514;Cesamet；CAS[51022-71-0]

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