tert-butyl (4S)-4-[[(benzyloxy)carbonyl]amino]-5-[(2,5-dioxo-1-pyrrolidinyl)oxy]-5-oxopentanoate -Drug Synthesis Database

【结构式】

【分子编号】51010

【品名】tert-butyl (4S)-4-[[(benzyloxy)carbonyl]amino]-5-[(2,5-dioxo-1-pyrrolidinyl)oxy]-5-oxopentanoate

【CA登记号】

【分子式】C₂₁H₂₆N₂O₈

【分子量】434.44612

【元素组成】C 58.06% H 6.03% N 6.45% O 29.46%

与该中间体有关的原料药合成路线共 2 条

合成路线1 合成路线2

合成路线1

该中间体在本合成路线中的序号：(XII)

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：(XVI)

Coupling of the succinimidyl ester of protected glutamic acid (XVI) with glutamic acid gamma-tert-butyl ester (XV) provided the protected dipeptide (XVII), which was then activated with tetrafluorophenol (XVIII) by means of EDC in DMF to yield the tetrafluorophenyl ester (XIX). Condensation of (XIX) with amine (XIV) produced amide (XX), whose N-benzyloxycarbonyl group was then removed by hydrogenolysis over Pd/C to yield amine (XXI).

参考文献中间体

合成目标

【1】 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	CAS号	分子式	供应商	用于合成
(XIV)	51008	(2S)-2-[[(4-[4-[(2-aminoethyl)amino]-4-oxobutoxy]-2,6-dimethylphenyl)sulfonyl]amino]-3-[([1-[3-(1H-imidazol-2-ylamino)propyl]-1H-indazol-5-yl]carbonyl)amino]propionic acid		C₃₁H₄₁N₉O₇S	详情	详情
(XV)	51009	(2S)-2-amino-5-(tert-butoxy)-5-oxopentanoic acid		C₉H₁₇NO₄	详情	详情
(XVI)	51010	tert-butyl (4S)-4-[[(benzyloxy)carbonyl]amino]-5-[(2,5-dioxo-1-pyrrolidinyl)oxy]-5-oxopentanoate		C₂₁H₂₆N₂O₈	详情	详情
(XVII)	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
(XVIII)	49986	2,3,5,6-Tetrafluorophenol	769-39-1	C₆H₂F₄O	详情	详情
(XIX)	51012	5-(tert-butyl) 1-(2,3,5,6-tetrafluorophenyl) (2S)-2-[[(2S)-2-[[(benzyloxy)carbonyl]amino]-5-(tert-butoxy)-5-oxopentanoyl]amino]pentanedioate		C₃₂H₃₈F₄N₂O₉	详情	详情
(XX)	51013	(2S)-2-([[4-([(10S,13S)-10,13-bis[3-(tert-butoxy)-3-oxopropyl]-4,9,12,15-tetraoxo-17-phenyl-16-oxa-5,8,11,14-tetraazaheptadec-1-yl]oxy)-2,6-dimethylphenyl]sulfonyl]amino)-3-[([1-[3-(1H-imidazol-2-ylamino)propyl]-1H-indazol-5-yl]carbonyl)amino]propionic acid		C₅₇H₇₇N₁₁O₁₅S	详情	详情
(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

Extended Information