4,4-dimethyl-3,5,8-trioxabicyclo[5.1.0]octane -Drug Synthesis Database

【结构式】

【分子编号】60022

【品名】4,4-dimethyl-3,5,8-trioxabicyclo[5.1.0]octane

【CA登记号】

【分子式】C₇H₁₂O₃

【分子量】144.17048

【元素组成】C 58.32% H 8.39% O 33.29%

与该中间体有关的原料药合成路线共 4 条

合成路线1 合成路线2 合成路线3 合成路线4

合成路线1

该中间体在本合成路线中的序号：(II)

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

参考文献中间体

合成目标

【1】 Gries, H.; Nickisch, K.; Platzek, J.; Börner, H.; Tilstam, U. (Schering AG); 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. DE 4218744; WO 9324469 .

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)	60022	4,4-dimethyl-3,5,8-trioxabicyclo[5.1.0]octane		C₇H₁₂O₃	详情	详情
(III)	60023	(5S,6R)-2,2-dimethyl-6-(1,4,7,10-tetraazacyclododecan-1-yl)-1,3-dioxepan-5-ol		C₁₅H₃₂N₄O₃	详情	详情
(IV)	60024	(2S,3R)-3-(1,4,7,10-tetraazacyclododecan-1-yl)-1,2,4-butanetriol		C₁₂H₂₈N₄O₃	详情	详情
(V)	60025	2-[4-[(1R,2S)-2,3-dihydroxy-1-(hydroxymethyl)propyl]-7,10-bis(2-hydroxy-2-oxoethyl)-1,4,7,10-tetraazacyclododecan-1-yl]acetic acid		C₁₈H₃₄N₄O₉	详情	详情

合成路线2

该中间体在本合成路线中的序号：(II)

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

参考文献中间体

合成目标

【1】 Blaszkiewicz, P.; Platzek, J.; Hoffmann, H.; Petrov, O. (Schering AG); Lithium complexes of N-(1-hydroxymethyl-2,3-dihydroxypropyl)-1,4,7-triscarboxymethyl-1,4,7,10-tetraazacyclododecane, production and use thereof. DE 10064467; WO 0248119 .
【2】 Blaszkiewicz, P.; Petrov, O. (Schering AG); Production of mono and 1,7-bis-N-hydroxyalkyl-cyclene and lithium salt complexes. DE 19724186; US 5994536; WO 9855467 .

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)	60022	4,4-dimethyl-3,5,8-trioxabicyclo[5.1.0]octane		C₇H₁₂O₃	详情	详情
(VI)	60026	lithium chloride (5S,6R)-2,2-dimethyl-6-(1,4,7,10-tetraazacyclododecan-1-yl)-1,3-dioxepan-5-ol		C₁₅H₃₂ClLiN₄O₃	详情	详情
(VII)	60027	lithium chloride 2-[4-[(1R,2S)-2,3-dihydroxy-1-(hydroxymethyl)propyl]-7,10-bis(2-hydroxy-2-oxoethyl)-1,4,7,10-tetraazacyclododecan-1-yl]acetic acid		C₁₈H₃₄ClLiN₄O₉	详情	详情

合成路线3

该中间体在本合成路线中的序号：(II)

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

参考文献中间体

合成目标

【1】 Murru, M.; Ripa, G.; Scala, A.; Viscardi, C.F.; Ausonio, M.; Scotti, C.; Cossuta, P. (Bracco SpA; Dibra SpA); A process for the preparation of macrocyclic chelants and the chelates thereof with paramagnetic metal ions. WO 9856775 .

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(A)	23660	2-Bromoacetic acid	79-08-3	C₂H₃BrO₂	详情	详情
(I)	14855	1,4,7,10-tetraazacyclododecane; Cyclen	294-90-6	C₈H₂₀N₄	详情	详情
(II)	60022	4,4-dimethyl-3,5,8-trioxabicyclo[5.1.0]octane		C₇H₁₂O₃	详情	详情
(VIII)	60028	octahydro-5H-2a,4a,7,9a-tetraazacycloocta[cd]pentalene		C₉H₁₈N₄	详情	详情
(IX)	60029	2-[4-formyl-7,10-bis(2-hydroxy-2-oxoethyl)-1,4,7,10-tetraazacyclododecan-1-yl]acetic acid		C₁₅H₂₆N₄O₇	详情	详情
(X)	60030	trisodium 2-[4,10-bis(2-oxido-2-oxoethyl)-1,4,7,10-tetraazacyclododecan-1-yl]acetate		C₁₄H₂₃N₄Na₃O₆	详情	详情
(XI)	60031	trisodium 2-[4-[(5R,6S)-6-hydroxy-2,2-dimethyl-1,3-dioxepan-5-yl]-7,10-bis(2-oxido-2-oxoethyl)-1,4,7,10-tetraazacyclododecan-1-yl]acetate		C₂₁H₃₅N₄Na₃O₉	详情	详情

合成路线4

该中间体在本合成路线中的序号：(II)

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

参考文献中间体

合成目标

【1】 Gries, H.; Platzek, J. (Schering AG); Process for the production of metal complexes of N-beta-hydroxyalkyl-tri-N-carboxyalkyl-1,4,7,10-tetraazacyclododecane and derivs. thereof. DE 4237943; EP 0596586 .

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(II)	60022	4,4-dimethyl-3,5,8-trioxabicyclo[5.1.0]octane		C₇H₁₂O₃	详情	详情
(III)	60023	(5S,6R)-2,2-dimethyl-6-(1,4,7,10-tetraazacyclododecan-1-yl)-1,3-dioxepan-5-ol		C₁₅H₃₂N₄O₃	详情	详情
(V)	60025	2-[4-[(1R,2S)-2,3-dihydroxy-1-(hydroxymethyl)propyl]-7,10-bis(2-hydroxy-2-oxoethyl)-1,4,7,10-tetraazacyclododecan-1-yl]acetic acid		C₁₈H₃₄N₄O₉	详情	详情
(VIII)	14855	1,4,7,10-tetraazacyclododecane; Cyclen	294-90-6	C₈H₂₀N₄	详情	详情
(XII)	60028	octahydro-5H-2a,4a,7,9a-tetraazacycloocta[cd]pentalene		C₉H₁₈N₄	详情	详情

Extended Information