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Nabumetone, BRL-14777, Nabuser, Listran, Relafen, Relifen, Arthaxan, Relifex

萘丁美酮Chemical Name: 4-(6-Methoxy-2-naphthalenyl)-2-butanone
CAS No. 42924-53-8
项目整合开发状态: Launched-1985
项目研究机构: GlaxoSmithKline (Originator), Procter & Gamble (Not Determined), Meda (Licensee), Uriach (Licensee)
合成路线:The silylation of 4-acetoxy-2-pyrrolidone (I) with trimethylchlorosilane (II) by means of triethyl amine in THF gives the corresponding N-trimethylsilyl derivative (III),which is condensed with 4-methoxybenzoyl chloride (IV) by means of NaHCO3 in THF yielding 1-(4-methoxybenzoyl)pyrrolin-2-one (V).Finally,this compound is reduced with H2 over Pd/C in ethyl acetate.

合成路线:The condensation of 4-aminobutyric acid (VI) with acid chloride (IV) by means of NaOH in water gives 4-(4-methoxybenzoylamino)butyric acid (VII),which is then cyclized by means of P2O5 in phosphoric acid.

合成路线:The condensation of 6-methoxy-2-naphthaldehyde (I) with acetone by means of NaOH in water gives 4-(6-methoxy-2-naphtyl)-3-buten-2-one (II),which is reduced with H2 over Pd/C in ethyl acetate.
📌 参考资料/链接:
参考文献标题:1-(p-Methoxy-p-hydroxy,and p-benzyloxybenzoyl)-2-pyrrolidinones
文献作者:Kyburz,E.; Aschwanden,W.(F.Hoffmann-La Roche AG)
参考来源:DD 141828; EP 0005143; EP 0044088; ES 477587; ES 483756; JP 54117468

📄 详细内容


合成路线:The condensation of 6-methoxy-2-naphthaldehyde (I) with ethyl aceto-acetate (II) gives ethyl 2-(6-methoxy-2-naphthylmethylene)acetoacetate (III),which is reduced to ethyl 2-(6-methoxy-2-naphthylmethyl)acetoacetate (IV).Finally,this compound is hydrolyzed and decarboxylated in acidic medium.

参考文献标题:A1 14777 by hydrogenation
文献作者:Rose,C.J.; Miller,D.(SmithKline Beecham plc)
参考来源:CA 1134384


合成路线:By condensation of 2-bromo-6-methoxynaphthalene (I) with 3-buten-2-ol (VI) catalyzed by Pd(OAc)2 or PdCl2,along with PPh3 and NaHCO3 in 1-methyl-2-pyrrolidone at 140 C.The reaction of 2-bromo-6-methoxynaphthalene (I) with Mg in THF gives the expected Grignard reagent (VII),which is then condensed with 3-buten-2-one (II) by means of ZnCl2-amine complex in the same solvent.

参考文献标题:Method of preparation of nabumetone
文献作者:Davenport,K.G.; Aslam,M.(Celanese AG)
参考来源:EP 0376516


合成路线:The condensation of 2-bromo-6-methoxynaphthalene (I) with 3-buten-2-one (II) by means of PdCl2,PPh3 and K2CO3 in DMF at 132 C gives 4-(6-methoxy-2-naphthyl)-3-buten-2-one (III),which is then hydrogenated with H2 over Pd/C in DMF.The same condensation can be performed with PdCl2 ,PPh3 and NaHCO3 in 1-methyl-2-pyrrolidone at 130 C.The reaction of 4-hydroxy-2-butanone (IV) with acetic anhydride or acetyl chloride gives 4-acetyl-2-butanone (V),which is condensed with 2-bromo-6-methoxynaphthalene (I) by means of PdCl2,PPh3 and K2CO3 in DMF at 132 C to yield the previously reported 4-(6-methoxy-2-naphthyl)-3-buten-2-one (III).

参考文献标题:Use of 4-substd.2-butanones to prepare nabumetone
文献作者:Fritch,J.R.; Rios,D.E.; Smith,J.C.; Aslam,M.(Celanese AG)
参考来源:WO 9640608


合成路线:The condensation of 6-methoxy-2-naphthaldehyde (I) with acetone by means of NaOH in water gives 4-(6-methoxy-2-naphtyl)-3-buten-2-one (II),which is reduced with H2 over Pd/C in ethyl acetate.

合成路线:The reduction of methyl 6-methoxy-2-naphtyl acetate (III) with LiAlH4 in refluxing ether gives 2-(6-methoxy-2-naphthyl)ethanol (IV),which by treatment with PBr3 in refluxing benzene is converted into 2-(6-methoxy-2-naphthyl)ethyl bromide (V).The reaction of (V) with KCN in refluxing ethanol - water affords 3-(6-methoxy-2-naphthyl)propionitrile (VI),which is finally treated with methylmagnesium iodide in refluxing ethanol.

参考文献标题:Nabumetone
文献作者:Neuman,M.; Blancafort,P.; Castar,J.; Serradell,M.N.
参考来源:Drugs Fut 1981,6(1),35


合成路线:A short,simple and economical process for large-scale preparation of nabumetone has been reported:Condensation of commercially available 2-acetyl-6-methoxynaphthalene (2-acetylnaroline) (I) with ethyl acetate (II) by means of potassium sec-butoxide (sec-BuOK) in DMSO gives the ketoenol (III),which is reduced with H2 over Pd/C in ethyl acetate with a catalytic amount of sulfuric acid.

参考文献标题:Process research and structural studies on nabumetone
文献作者:Nageshwar,D.; Devi,A.S.; Reddy,G.O.; Sarma,M.R.; Reddy,G.B.; Vyas,K.; Prabhakar,C.; Reddy,C.M.; Babu,J.M.
参考来源:Org Process Res Dev 1999,3(2),121


合成路线:The condensation of 6-methoxy-2-naphthaldehyde (I) with acetone by means of NaOH in water gives 4-(6-methoxy-2-naphtyl)-3-buten-2-one (II),which is reduced with H2 over Pd/C in ethyl acetate.

合成路线:The reduction of methyl 6-methoxy-2-naphtyl acetate (III) with LiAlH4 in refluxing ether gives 2-(6-methoxy-2-naphthyl)ethanol (IV),which by treatment with PBr3 in refluxing benzene is converted into 2-(6-methoxy-2-naphthyl)ethyl bromide (V).The reaction of (V) with KCN in refluxing ethanol - water affords 3-(6-methoxy-2-naphthyl)propionitrile (VI),which is finally treated with methylmagnesium iodide in refluxing ethanol.

参考文献标题:4-(6-Methoxy-2-naphtyl)butan-2-one and related analogues,a novel structural class of antiinflammatory compounds
文献作者:Goudie,A.C.Ert al.; Gaster,L.M.; Lake,A.W.; Rose,C.J.; Freeman,P.C.; Hughes,B.O.; Miller,D.B.
参考来源:J Med Chem 1978,21(12),1260


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