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Gadobutrol, SH-L-562, Gadovist

钆布醇Chemical Name: [10-[(1RS,2SR)-2,3-Dihydroxy-1-(hydroxymethyl)propyl]-1,4,7,10-tetraazacyclodecane-1,4,7-triacetato(3-)]gadolinium
CAS No. 138071-82-6
项目整合开发状态: Launched-1998
项目研究机构: Schering AG (Originator)
合成路线:In a related method for obtaining the precursor (V),epoxide (II) was condensed with the tosyl-protected tetraamine (XIII) in an autoclave at 170 C to give (XIV).The N-tosyl groups of (XIV) were then removed by treatment with lithium metal in liquid ammonia,yielding intermediate (III),which was then subjected to alkylation with bromoacetic acid,followed by acid hydrolysis
📌 参考资料/链接:
参考文献标题:1,4,7,10-Tetraazacyclododecane-butyl-triols,process for their preparation,and pharmaceutical agents containing these cpds.
文献作者:Platzek,J.; Gries,H.; Weinmann,H.-J.; Schuhmann-Giampieri,G.; Press,W.-R.(Schering AG)
参考来源:DE 4009119; EP 0448191; US 2002176823; US 6399043

📄 详细内容


合成路线:A different synthesis started from the previously reported tetraaza cyclopentaacenaphthylene (XV).Treatment of (XV) with a solution of piperazine at pH 6 gave rise to the bicyclic lactam (XVI).Alkylation of (XVI) with bromoacetic acid,followed by basic lactam hydrolysis furnished the tris(carboxymethyl) derivative (X),which was processed as in Scheme 3.

参考文献标题:1,4,7,10-Tetraazabicyclo[8.2.2]tetradecan-2-one,a process for the preparation thereof and the use thereof for the preparation of tetraazamacrocycles
文献作者:Argese,M.; Ripa,G.(Bracco SpA; Dibra SpA)
参考来源:EP 0998476; JP 2002511884; WO 9905145


合成路线:1,4,7,10-Tetraazacyclododecane (I) was condensed with 2,3-epoxy-1,4-butanediol acetonide (II) in boiling n-butanol to afford adduct (III).Subsequent acetonide (III) hydrolysis in the presence of HCl led to triol (IV).Alkylation of (IV) with chloroacetic acid furnished the tetraaminotricarboxylic acid (V).Alternatively,compound (V) was prepared by alkylation of (III) with chloroacetic acid,followed by acidic ketal hydrolysis.The title gadolinium complex was finally prepared by treatment of the cyclic tetraamine (V) with gadolinium oxide

参考文献标题:Process for producing N-beta-hydroxyalkyl-tri-N-carboxyalkyl-1,4,7,10-tetraazacyclododecane and N-beta-hydroxyalkyl-tri-N-carboxyalkyl-1,4,8,11-tetraazacyclotetradecane derivs.and their metal complexes
文献作者:Gries,H.; Nickisch,K.; Platzek,J.; Bner,H.; Tilstam,U.(Schering AG)
参考来源:DE 4218744; WO 9324469


合成路线:Alternatively,the protected tetraamine (VIII) was condensed with epoxide (II) to afford (XII),which was further hydrolyzed to the mono-substituted tetraazacyclododecane (III) under basic conditions.Alkylation of (III) with chloracetic acid,followed by acidic ketal hydrolysis furnished the precursor (V),which was finally complexed with gadolinium oxide as above

参考文献标题:Process for the production of metal complexes of N-beta-hydroxyalkyl-tri-N-carboxyalkyl-1,4,7,10-tetraazacyclododecane and derivs.thereof
文献作者:Gries,H.; Platzek,J.(Schering AG)
参考来源:DE 4237943; EP 0596586


合成路线:In a similar procedure,condensation of (I) with epoxide (II) in isopropanol in the presence of LiCl furnished the corresponding adduct as a complex with LiCl (VI) (2).Condensation of (VI) with chloroacetic acid,followed by acidic hydrolysis provided the lithium complex (VII).Finally,treatment of (VII) with Gd2O3 and HCl afforded the title gadolinium compound

参考文献标题:Production of mono and 1,7-bis-N-hydroxyalkyl-cyclene and lithium salt complexes
文献作者:Blaszkiewicz,P.; Petrov,O.(Schering AG)
参考来源:DE 19724186; US 5994536; WO 9855467


合成路线:The macrocyclic tetraamine (I) was protected as the triaminomethane derivative (VIII) by treatment with either triethyl orthoformate (4) or with dimethylformamide dimethylacetal (5).Alkylation of (VIII) with bromoacetic acid gave rise to the N-formyl N',N'',N'''-tris(carboxymethyl) compound (IX).After basic hydrolysis of the formamide function of (IX),the resultant N-deprotected amine (X) was condensed with epoxide (II) to yield (XI).Further complexation with GdCl3 and ketal group hydrolysis led to the target compound

参考文献标题:A process for the preparation of macrocyclic chelants and the chelates thereof with paramagnetic metal ions
文献作者:Murru,M.; Ripa,G.; Scala,A.; Viscardi,C.F.; Ausonio,M.; Scotti,C.; Cossuta,P.(Bracco SpA; Dibra SpA)
参考来源:WO 9856775


合成路线:In a similar procedure,condensation of (I) with epoxide (II) in isopropanol in the presence of LiCl furnished the corresponding adduct as a complex with LiCl (VI) (2).Condensation of (VI) with chloroacetic acid,followed by acidic hydrolysis provided the lithium complex (VII).Finally,treatment of (VII) with Gd2O3 and HCl afforded the title gadolinium compound
参考文献标题:Lithium complexes of N-(1-hydroxymethyl-2,3-dihydroxypropyl)-1,4,7-triscarboxymethyl-1,4,7,10-tetraazacyclododecane,production and use thereof
文献作者:Blaszkiewicz,P.; Platzek,J.; Hoffmann,H.; Petrov,O.(Schering AG)
参考来源:DE 10064467; WO 0248119


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