合成路线:The reaction of 2-chloropyridine (I) with 2-(methyl-amino)ethanol (II) by heating at 150 C gives 2-[N-methyl-N-(2-pyridyl)amino]ethanol (III),which is condensed with 4-fluorobenzaldehyde (IV) by means of NaH in DMF,yielding 4-[2-[N-methyl-N-(2-pyridyl)amino]-ethoxy]benzaldehyde (V) (1-3).The reaction of (V) with thiazolidine-2,4-dione (VI) by means of piperidinium acetate in refluxing toluene affords 5-[4-[2-[N-methyl-N-(2-pyridyl)- amino]ethoxy]benzylidene]thiazolidine-2,4-dione (VII).Finally,this compound is reduced with H2 over Pd/C (1),Mg in methanol (2,3) or biocatalytically by incubation with whole cells of the yeast Rhodotorula rubra CBS 6469 at pH 7.5-8.0 (4-6).Under acidic conditions,pH 3.0-5.0,this microbial biotransformation is enantioselective,giving the (+)-(R)-enantiomer of rosiglitazone.
参考文献标题:Process for the preparation of pharmaceutically active thiazolidine or oxazolidine cpds.by a yeast reductase
文献作者:Hindley,R.M.; Woroniecki,S.R.(SmithKline Beecham plc)
参考来源:WO 9310254
合成路线:The reaction of 2-chloropyridine (I) with 2-(methyl-amino)ethanol (II) by heating at 150 C gives 2-[N-methyl-N-(2-pyridyl)amino]ethanol (III),which is condensed with 4-fluorobenzaldehyde (IV) by means of NaH in DMF,yielding 4-[2-[N-methyl-N-(2-pyridyl)amino]-ethoxy]benzaldehyde (V) (1-3).The reaction of (V) with thiazolidine-2,4-dione (VI) by means of piperidinium acetate in refluxing toluene affords 5-[4-[2-[N-methyl-N-(2-pyridyl)- amino]ethoxy]benzylidene]thiazolidine-2,4-dione (VII).Finally,this compound is reduced with H2 over Pd/C (1),Mg in methanol (2,3) or biocatalytically by incubation with whole cells of the yeast Rhodotorula rubra CBS 6469 at pH 7.5-8.0 (4-6).Under acidic conditions,pH 3.0-5.0,this microbial biotransformation is enantioselective,giving the (+)-(R)-enantiomer of rosiglitazone.
参考文献标题:Process for the preparation of rosiglitazone maleate
文献作者:Vyas,S.K.(Torrent Pharmaceuticals Ltd.)
参考来源:US 2002115866; US 6515132; WO 0251823
合成路线:The reaction of 2-chloropyridine (I) with 2-(methyl-amino)ethanol (II) by heating at 150 C gives 2-[N-methyl-N-(2-pyridyl)amino]ethanol (III),which is condensed with 4-fluorobenzaldehyde (IV) by means of NaH in DMF,yielding 4-[2-[N-methyl-N-(2-pyridyl)amino]-ethoxy]benzaldehyde (V) (1-3).The reaction of (V) with thiazolidine-2,4-dione (VI) by means of piperidinium acetate in refluxing toluene affords 5-[4-[2-[N-methyl-N-(2-pyridyl)- amino]ethoxy]benzylidene]thiazolidine-2,4-dione (VII).Finally,this compound is reduced with H2 over Pd/C (1),Mg in methanol (2,3) or biocatalytically by incubation with whole cells of the yeast Rhodotorula rubra CBS 6469 at pH 7.5-8.0 (4-6).Under acidic conditions,pH 3.0-5.0,this microbial biotransformation is enantioselective,giving the (+)-(R)-enantiomer of rosiglitazone.
参考文献标题:The synthesis of BRL 49653 - A novel and potent antihyperglycaemic agent
文献作者:Smith,S.A.; Thurlby,P.L.; Cantello,B.C.C.; Haigh,D.; Cawthorne,M.A.; Hindley,R.M.
参考来源:Bioorg Med Chem Lett 1994,4(10),1181-4
合成路线:The reaction of 2-chloropyridine (I) with 2-(methyl-amino)ethanol (II) by heating at 150 C gives 2-[N-methyl-N-(2-pyridyl)amino]ethanol (III),which is condensed with 4-fluorobenzaldehyde (IV) by means of NaH in DMF,yielding 4-[2-[N-methyl-N-(2-pyridyl)amino]-ethoxy]benzaldehyde (V) (1-3).The reaction of (V) with thiazolidine-2,4-dione (VI) by means of piperidinium acetate in refluxing toluene affords 5-[4-[2-[N-methyl-N-(2-pyridyl)- amino]ethoxy]benzylidene]thiazolidine-2,4-dione (VII).Finally,this compound is reduced with H2 over Pd/C (1),Mg in methanol (2,3) or biocatalytically by incubation with whole cells of the yeast Rhodotorula rubra CBS 6469 at pH 7.5-8.0 (4-6).Under acidic conditions,pH 3.0-5.0,this microbial biotransformation is enantioselective,giving the (+)-(R)-enantiomer of rosiglitazone.
参考文献标题:[[*-(Heterocyclylamino)alkoxy]benzyl]-2,4-thiazolidinediones as potent antihyperglycemic agents
文献作者:Cantello,BB.C.C.; Cawthorne,M.A.; Cottam,G.P.; Duff,P.T.; Haigh,D.; Hindley,R.M.; Lister,C.A.; Smith,S.A.; Thurlby,P.L.
参考来源:J Med Chem 1994,37(23),3977-85
合成路线:The reaction of 2-chloropyridine (I) with 2-(methyl-amino)ethanol (II) by heating at 150 C gives 2-[N-methyl-N-(2-pyridyl)amino]ethanol (III),which is condensed with 4-fluorobenzaldehyde (IV) by means of NaH in DMF,yielding 4-[2-[N-methyl-N-(2-pyridyl)amino]-ethoxy]benzaldehyde (V) (1-3).The reaction of (V) with thiazolidine-2,4-dione (VI) by means of piperidinium acetate in refluxing toluene affords 5-[4-[2-[N-methyl-N-(2-pyridyl)- amino]ethoxy]benzylidene]thiazolidine-2,4-dione (VII).Finally,this compound is reduced with H2 over Pd/C (1),Mg in methanol (2,3) or biocatalytically by incubation with whole cells of the yeast Rhodotorula rubra CBS 6469 at pH 7.5-8.0 (4-6).Under acidic conditions,pH 3.0-5.0,this microbial biotransformation is enantioselective,giving the (+)-(R)-enantiomer of rosiglitazone.
参考文献标题:Facile biocatalytic reduction of the carbon-carbon double bond of 5-benzylidenethiazolidine-2,4-diones.Synthesis of (?-5-(4-(2-[methyl(2-pyridyl)amino]ethoxy)benzyl)-thiazolidine-2,4-dione (BRL 49653),its (R)-(?-enantiomer and analogues
文献作者:Cantello,B.C.C.; Haigh,D.; Eggleston,D.S.; Jennings,K.R.; Heath,C.M.; Sime,J.T.; Haltiwanger,R.C.; Woroniecki,S.R.; Hindley,R.M.
参考来源:J Chem Soc - Perkins Trans I 1994,22(22),3319-24
合成路线:The reaction of 2-chloropyridine (I) with 2-(methyl-amino)ethanol (II) by heating at 150 C gives 2-[N-methyl-N-(2-pyridyl)amino]ethanol (III),which is condensed with 4-fluorobenzaldehyde (IV) by means of NaH in DMF,yielding 4-[2-[N-methyl-N-(2-pyridyl)amino]-ethoxy]benzaldehyde (V) (1-3).The reaction of (V) with thiazolidine-2,4-dione (VI) by means of piperidinium acetate in refluxing toluene affords 5-[4-[2-[N-methyl-N-(2-pyridyl)- amino]ethoxy]benzylidene]thiazolidine-2,4-dione (VII).Finally,this compound is reduced with H2 over Pd/C (1),Mg in methanol (2,3) or biocatalytically by incubation with whole cells of the yeast Rhodotorula rubra CBS 6469 at pH 7.5-8.0 (4-6).Under acidic conditions,pH 3.0-5.0,this microbial biotransformation is enantioselective,giving the (+)-(R)-enantiomer of rosiglitazone.
参考文献标题:Rosiglitazone Maleate
文献作者:Sorbera,L.A.; Rabasseda,X.; Leeson,P.A.
参考来源:Drugs Fut 1998,23(9),977
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