2-[4,10-bis(2-hydroxy-2-oxoethyl)-7-(2-hydroxypropyl)-1,4,7,10-tetraazacyclododecan-1-yl]acetic acid -Drug Synthesis Database

【结构式】

【分子编号】14858

【品名】2-[4,10-bis(2-hydroxy-2-oxoethyl)-7-(2-hydroxypropyl)-1,4,7,10-tetraazacyclododecan-1-yl]acetic acid

【CA登记号】

【分子式】C₁₇H₃₂N₄O₇

【分子量】404.46384

【元素组成】C 50.48% H 7.97% N 13.85% O 27.69%

与该中间体有关的原料药合成路线共 1 条

合成路线1

该中间体在本合成路线中的序号：(IV)

The synthesis of gadoteridol is as follows: Compound (I) was reacted with DMF dimethylacetal to form the tricyclic intermediate (II). Following partial hydrolysis of (II), (III) was obtained and isolated in high quality and yield. (III) was reacted with tert-butyl bromoacetate in a basic media to obtain (IV), which was treated with aqueous sulfuric acid to effect removal of the tert-butyl and formyl protecting groups. (V) could be either crystallized or lyophilized. (V) was reacted with propylene oxide at pH 12 and excess propylene oxide was removed under vacuum upon completion of the reaction. (VI) was isolated by anion exchange chromatography with sulfate, and sulfate was then removed using a poly(4-vinylpyridine) resin. HP-DO3A was reacted with gadolinium oxide in water. Following concentration, excess gadolinium oxide was removed by filtration, and Gd(HP-DO3A)H2O was isolated by removing solvent. The product was then crystallized from methanol/acetone.

参考文献中间体

合成目标

【1】 Emswiler, J.E.; Gaughan, G.T.; Delaney, E.J.; Prasad, J.S.; Tweedle, M.F.; Dischino, D.D.; Srivastava, S.K.; Synthesis of nonionic gadolinium chelates useful as contrast agents for magnetic resonance imaging: 1,4,7 Tris(carboxymethyl)-10-substituted-1,4,7,10-tetraazacyclodecanes and their corresponding gadolinium chelates. Inorg Chem 1991, 30, 6, 1265-9.
【2】 Runge, V.M.; Tweedle, M.F.; Gadoteridol. Drugs Fut 1992, 17, 3, 187.

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(I)	14855	1,4,7,10-tetraazacyclododecane; Cyclen	294-90-6	C₈H₂₀N₄	详情	详情
(II)	14856	octahydro-5H-2a,4a,7,9a-tetraazacycloocta[cd]pentalene		C₉H₁₈N₄	详情	详情
(III)	14857	1,4,7,10-tetraazacyclododecane-1-carbaldehyde		C₉H₂₀N₄O	详情	详情
(IV)	14858	2-[4,10-bis(2-hydroxy-2-oxoethyl)-7-(2-hydroxypropyl)-1,4,7,10-tetraazacyclododecan-1-yl]acetic acid		C₁₇H₃₂N₄O₇	详情	详情
(V)	14859	2-[4,10-bis(2-hydroxy-2-oxoethyl)-1,4,7,10-tetraazacyclododecan-1-yl]acetic acid		C₁₄H₂₆N₄O₆	详情	详情
(VI)	14860	tert-butyl 2-[4,10-bis[2-(tert-butoxy)-2-oxoethyl]-7-formyl-1,4,7,10-tetraazacyclododecan-1-yl]acetate		C₂₇H₅₀N₄O₇	详情	详情

Extended Information