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项目整合精选>>>Gadoxetic acid disodium salt, Gadoxate disodium, Gd-EOB-DTPA(undefined isomer), Primovist, Eovist
Gadoxetic acid disodium salt, Gadoxate disodium, Gd-EOB-DTPA(undefined isomer), Primovist, Eovist
钆塞酸Chemical Name: Disodium [3,6,9-tris(carboxymethyl)-4(S)-(4-ethoxybenzyl)-3,6,9-triazaundecane-1,11-dioate(5-)]gadolinate(2-)
CAS No. 135326-11-3 (free acid)
项目整合开发状态: Launched-2004
项目研究机构: Schering AG (Originator)
合成路线:The acylation of O-benzyltyrosine (I) with ethyl trifluoroacetate in methanol gives O-benzyl-N-trifluroacetyltyrosine (II),which is condensed with N-(2-aminoethyl)carbamic acid benzyl ester (III) by means of ethyl chloroformate in THF,yielding the tyrosinamide (IV).The deacylation of (IV) by means of NaBH4 in ethanol affords the N-deprotected tyrosinamide (V),which is submitted to hydrogenolysis with H2 over Pd/C in methanol to provide tyrosine 2-aminoethylamide (VI).The reduction of (VI) with diborane gives 3-aza-1-(4-hydroxybenzyl)pentane-1,5-diamine (VII),which is alkylated with bromoacetic acid tert-butyl ester (VIII) and NaHCO3 to yield the 1-(4-hydroxybenzyl)-3-azapentane-1,5-diamine N,N,N'.N'',N''-pentaacetate penta-tert-butyl ester (IX) (1).The alkylation of the OH group of (IX) with ethyl iodide and NaH in THF affords the corresponding ethoxybenzyl derivative (X),which is treated with TFA to provide the pentaacetic acid derivative (XI).Finally,this compound is complexed with Gd2O3 and NaOH in hot water to furnish the target gadolinium complex.
📌 参考资料/链接：
参考文献标题:Substd.complex-builders,complexes and complex salts,process for their preparation and pharmaceutical compsns.containing them
文献作者:Deutsch,J.; Gries,H.; Klieger,E.; Niedballa,U.; Renneke,F.J.; Conrad,J.; Mzel,W.(Schering AG)
参考来源:DE 3710730; WO 8807521
📄 详细内容
合成路线:The acylation of O-benzyltyrosine (I) with ethyl trifluoroacetate in methanol gives O-benzyl-N-trifluroacetyltyrosine (II),which is condensed with N-(2-aminoethyl)carbamic acid benzyl ester (III) by means of ethyl chloroformate in THF,yielding the tyrosinamide (IV).The deacylation of (IV) by means of NaBH4 in ethanol affords the N-deprotected tyrosinamide (V),which is submitted to hydrogenolysis with H2 over Pd/C in methanol to provide tyrosine 2-aminoethylamide (VI).The reduction of (VI) with diborane gives 3-aza-1-(4-hydroxybenzyl)pentane-1,5-diamine (VII),which is alkylated with bromoacetic acid tert-butyl ester (VIII) and NaHCO3 to yield the 1-(4-hydroxybenzyl)-3-azapentane-1,5-diamine N,N,N'.N'',N''-pentaacetate penta-tert-butyl ester (IX) (1).The alkylation of the OH group of (IX) with ethyl iodide and NaH in THF affords the corresponding ethoxybenzyl derivative (X),which is treated with TFA to provide the pentaacetic acid derivative (XI).Finally,this compound is complexed with Gd2O3 and NaOH in hot water to furnish the target gadolinium complex.
合成路线:The title complex was prepared starting from the previously described diethylenetriamino pentaacetate ester (I).Alkylation of the phenolic hydroxyl with iodoethane and NaH gave the ethyl ether (II).Subsequent trifluoroacetic acid-promoted cleavage of the tert-butyl esters yielded the penta-carboxylic acid (III).Finally,complexation of (III) with Gd2O3,followed by neutralization with NaOH furnished the target compound
参考文献标题:DTPA-complexes derivs.,pharmaceutical compsns.containing them,their use and process for their preparation
文献作者:Schmitt-Willich,H.; Platzek,J.; Gries,H.; Schuhmann-Giampieri,G.; Vogler,H.; Weinmann,H.-J.(Schering AG)
参考来源:AU 9058024; DE 3922005; EP 0405704; JP 1991215457; US 5695739; US 6039931
产品链接: CAS No. 135326-11-3››