2-[4,7,10-tris[2-(tert-butoxy)-2-oxoethyl]-1,4,7,10-tetraazacyclododecan-1-yl]acetic acid -Drug Synthesis Database

【结构式】

【分子编号】51014

【品名】2-[4,7,10-tris[2-(tert-butoxy)-2-oxoethyl]-1,4,7,10-tetraazacyclododecan-1-yl]acetic acid

【CA登记号】

【分子式】C₂₈H₅₂N₄O₈

【分子量】572.74304

【元素组成】C 58.72% H 9.15% N 9.78% O 22.35%

与该中间体有关的原料药合成路线共 3 条

合成路线1 合成路线2 合成路线3

合成路线1

该中间体在本合成路线中的序号：(XV)

Coupling between gamma-tert-butoxy glutamic acid (XI) and gamma-tert-butoxy-N-Cbz-glutamic acid succinimidyl ester (XII) produced the protected dipeptide (XIII). This was further coupled to the intermediate amine (X) to furnish the corresponding amide (XIV). After hydrogenolysis of the N-Cbz protecting group of (XIV), the resultant amine (XV) was acylated with tetraazacyclododecanetetraacetic acid tri-tert-butyl ester (XVI), yielding the amide adduct (XVII).

参考文献中间体

合成目标

【1】 Cheesman, E.H.; et al.; Nonpeptide vitronectin antagonists labeled with Tc99m for imaging tumors. 222nd ACS Natl Meet (Aug 26 2001, Chicago) 2001, Abst MEDI 77.
【2】 Sworin, M.; Cheesman, E.H.; Rajopadhyem, M. (DuPont Pharmaceuticals Co.); Vitronectin receptor antagonist pharmaceuticals. EP 1140864; WO 0035887 .

中间体序号	中间体编号	品名	分子式	供应商	用于合成
(X)	52482	methyl 2-(4-(3-aminopropyl)-7-{[(1H-benzimidazol-2-ylmethyl)(methyl)amino]carbonyl}-3-oxo-2,3,4,5-tetrahydro-1H-1,4-benzodiazepin-2-yl)acetate	C₂₅H₃₀N₆O₄	详情	详情
(XI)	51009	(2S)-2-amino-5-(tert-butoxy)-5-oxopentanoic acid	C₉H₁₇NO₄	详情	详情
(XII)	51010	tert-butyl (4S)-4-[[(benzyloxy)carbonyl]amino]-5-[(2,5-dioxo-1-pyrrolidinyl)oxy]-5-oxopentanoate	C₂₁H₂₆N₂O₈	详情	详情
(XIII)	51011	(2S)-2-[[(2S)-2-[[(benzyloxy)carbonyl]amino]-5-(tert-butoxy)-5-oxopentanoyl]amino]-5-(tert-butoxy)-5-oxopentanoic acid	C₂₆H₃₈N₂O₉	详情	详情
(XIV)	52486		C₅₁H₆₆N₈O₁₂	详情	详情
(XV)	51014	2-[4,7,10-tris[2-(tert-butoxy)-2-oxoethyl]-1,4,7,10-tetraazacyclododecan-1-yl]acetic acid	C₂₈H₅₂N₄O₈	详情	详情
(XVI)	52483		C₄₃H₆₀N₈O₁₀	详情	详情
(XVII)	52484		C₇₁H₁₁₀N₁₂O₁₇	详情	详情

合成路线2

该中间体在本合成路线中的序号：(XXII)

Acylation of amine (XXI) with tetraazacyclododecanetetraacetic acid tri-tert-butyl ester (XXII) produced amide (XXIII) (1). After acidic cleavage of the tert-butyl ester groups of (XXIII), the resultant macrocyclic tetraamine (XXIV) was complexed with 111InCl3 in the presence of NH4OAc buffer to furnish the title indium-111 complex.

参考文献中间体

合成目标

【1】 Cheesman, E.H.; et al.; Nonpeptide vitronectin antagonists labeles with in-111 for imaging tumors. 222nd ACS Natl Meet (Aug 26 2001, Chicago) 2001, Abst MEDI 88.
【2】 Rajopadhye, M.; Harris, T.D.; Cheesman, E.H. (DuPont Pharmaceuticals Co.); Vitronectin receptor antagonist pharmaceuticals. WO 0035488 .

中间体序号	中间体编号	品名	分子式	供应商	用于合成
(XXI)	51021	(2S)-2-([[4-([(10S,13S)-13-amino-10-[3-(tert-butoxy)-3-oxopropyl]-18,18-dimethyl-4,9,12,16-tetraoxo-17-oxa-5,8,11-triazanonadec-1-yl]oxy)-2,6-dimethylphenyl]sulfonyl]amino)-3-[([1-[3-(1H-imidazol-2-ylamino)propyl]-1H-indazol-5-yl]carbonyl)amino]propionic acid	C₄₉H₇₁N₁₁O₁₃S	详情	详情
(XXII)	51014	2-[4,7,10-tris[2-(tert-butoxy)-2-oxoethyl]-1,4,7,10-tetraazacyclododecan-1-yl]acetic acid	C₂₈H₅₂N₄O₈	详情	详情
(XXIII)	51015	(2S)-2-([[4-([(10S,13S)-10-[3-(tert-butoxy)-3-oxopropyl]-18,18-dimethyl-4,9,12,16-tetraoxo-13-[(2-[4,7,10-tris[2-(tert-butoxy)-2-oxoethyl]-1,4,7,10-tetraazacyclododecan-1-yl]acetyl)oxy]-17-oxa-5,8,11-triazanonadec-1-yl]oxy)-2,6-dimethylphenyl]sulfonyl]amino)-3-[([1-[3-(1H-imidazol-2-ylamino)propyl]-1H-indazol-5-yl]carbonyl)amino]propionic acid	C₇₇H₁₂₀N₁₄O₂₁S	详情	详情
(XXIV)	51016	(4S)-5-([(1S)-3-carboxy-1-[([2-[(4-[4-[([(1S)-1-carboxy-2-[([1-[3-(1H-imidazol-2-ylamino)propyl]-1H-indazol-5-yl]carbonyl)amino]ethyl]amino)sulfonyl]-3,5-dimethylphenoxy]butanoyl)amino]ethyl]amino)carbonyl]propyl]amino)-5-oxo-4-([2-[4,7,10-tris(carboxymethyl)-1,4,7,10-tetraazacyclododecan-1-yl]acetyl]oxy)pentanoic acid	C₅₇H₈₀N₁₄O₂₁S	详情	详情

合成路线3

该中间体在本合成路线中的序号：(XXII)

Coupling of (XXVII) with the macrocyclic tetraacetic acid tri-tert-butyl ester (XXII) produced amide (XXVIII). Basic hydrolysis of the methyl ester group of (XXVIII), followed by acidic cleavage of the remaining protecting groups, furnished intermediate (XXIV), which was finally complexed as above.

参考文献中间体

合成目标

【1】 Cheesman, E.H.; et al.; Nonpeptide vitronectin antagonists labeles with in-111 for imaging tumors. 222nd ACS Natl Meet (Aug 26 2001, Chicago) 2001, Abst MEDI 88.

中间体序号	中间体编号	品名	分子式	供应商	用于合成
(XXII)	51014	2-[4,7,10-tris[2-(tert-butoxy)-2-oxoethyl]-1,4,7,10-tetraazacyclododecan-1-yl]acetic acid	C₂₈H₅₂N₄O₈	详情	详情
(XXIV)	51016	(4S)-5-([(1S)-3-carboxy-1-[([2-[(4-[4-[([(1S)-1-carboxy-2-[([1-[3-(1H-imidazol-2-ylamino)propyl]-1H-indazol-5-yl]carbonyl)amino]ethyl]amino)sulfonyl]-3,5-dimethylphenoxy]butanoyl)amino]ethyl]amino)carbonyl]propyl]amino)-5-oxo-4-([2-[4,7,10-tris(carboxymethyl)-1,4,7,10-tetraazacyclododecan-1-yl]acetyl]oxy)pentanoic acid	C₅₇H₈₀N₁₄O₂₁S	详情	详情
(XXVII)	51019	tert-butyl (4S)-4-amino-5-[[(1S)-4-(tert-butoxy)-1-([[2-([4-[4-([[(1S)-2-methoxy-2-oxo-1-([[(1-[3-[(1-trityl-1H-imidazol-2-yl)amino]propyl]-1H-indazol-5-yl)carbonyl]amino]methyl)ethyl]amino]sulfonyl)-3,5-dimethylphenoxy]butanoyl]amino)ethyl]amino]carbonyl)-4-oxobutyl]amino]-5-oxopentanoate	C₆₉H₈₇N₁₁O₁₃S	详情	详情
(XXVIII)	51020	tert-butyl (4S)-5-[[(1S)-4-(tert-butoxy)-1-([[2-([4-[4-([[(1S)-2-methoxy-2-oxo-1-([[(1-[3-[(1-trityl-1H-imidazol-2-yl)amino]propyl]-1H-indazol-5-yl)carbonyl]amino]methyl)ethyl]amino]sulfonyl)-3,5-dimethylphenoxy]butanoyl]amino)ethyl]amino]carbonyl)-4-oxobutyl]amino]-5-oxo-4-[(2-[4,7,10-tris[2-(tert-butoxy)-2-oxoethyl]-1,4,7,10-tetraazacyclododecan-1-yl]acetyl)amino]pentanoate	C₉₇H₁₃₇N₁₅O₂₀S	详情	详情

Extended Information