(4R)-2,6-dioxohexahydro-4-pyrimidinecarboxylic acid -Drug Synthesis Database

【结构式】

【分子编号】46755

【品名】(4R)-2,6-dioxohexahydro-4-pyrimidinecarboxylic acid

【CA登记号】

【分子式】C₅H₆N₂O₄

【分子量】158.11372

【元素组成】C 37.98% H 3.82% N 17.72% O 40.48%

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：(XVI)

Further coupling with N-alpha-Boc-L-4-(Fmoc-amino)phenylalanine (XIV), followed by Fmoc deprotection with piperidine, furnished (XV). The aniline derivative (XV) was acylated with L-hydroorotic acid (XVI) to yield, after Boc group cleavage, resin (XVII). Coupling of (XVII) with N-Boc-L-serine(O-benzyl) (XVIII) and subsequent deprotection gave (XIX).

参考文献中间体

合成目标

【1】 Stalewski, J.; Galyean, R.; Jiang, G.; et al.; GnRH antagonists: A new generation of long acting analogues incorporating p-ureido-phenylalanines at positions 5 and 6. J Med Chem 2001, 44, 3, 453.
【2】 Jiang, G.; Semple, G. (Ferring BV Group Holding); GnRH antagonists being modified in positions 5 and 6. WO 9846634 .

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(XVIIII)	16886	(2S)-3-(benzyloxy)-2-[(tert-butoxycarbonyl)amino]propionic acid; N-alpha-t-BOC-o-benzyl-L-serine	23680-31-1	C₁₅H₂₁NO₅	详情	详情
(XIII)	46749	benzyl (5S)-5-[((2S)-2-[[(2R)-2-amino-3-(4-[[(tert-butylamino)carbonyl]amino]phenyl)propanoyl]amino]-4-methylpentanoyl)amino]-6-[(2S)-2-([[(1R)-2-amino-1-methyl-2-oxoethyl]amino]carbonyl)pyrrolidinyl]-6-oxohexyl(isopropyl)carbamate		C₄₅H₆₉N₉O₈	详情	详情
(XIV)	46753	(2S)-3-(4-aminophenyl)-2-[(tert-butoxycarbonyl)amino]propionic acid	55533-24-9	C₁₄H₂₀N₂O₄	详情	详情
(XV)	46754	benzyl (5S,8S,11R,14S)-14-(4-aminobenzyl)-5-[[(2S)-2-([[(1R)-2-amino-1-methyl-2-oxoethyl]amino]carbonyl)pyrrolidinyl]carbonyl]-11-(4-[[(tert-butylamino)carbonyl]amino]benzyl)-8-isobutyl-18,18-dimethyl-7,10,13,16-tetraoxo-17-oxa-6,9,12,15-tetraazanonadec-1-yl(isopropyl)carbamate		C₅₉H₈₇N₁₁O₁₁	详情	详情
(XVI)	46755	(4R)-2,6-dioxohexahydro-4-pyrimidinecarboxylic acid		C₅H₆N₂O₄	详情	详情
(XVII)	46756	benzyl (5S)-5-[((2S)-2-[[(2R)-2-([(2S)-2-amino-3-[4-([[(4R)-2,6-dioxohexahydro-4-pyrimidinyl]carbonyl]amino)phenyl]propanoyl]amino)-3-(4-[[(tert-butylamino)carbonyl]amino]phenyl)propanoyl]amino]-4-methylpentanoyl)amino]-6-[(2S)-2-([[(1R)-2-amino-1-methyl-2-oxoethyl]amino]carbonyl)pyrrolidinyl]-6-oxohexyl(isopropyl)carbamate		C₅₉H₈₃N₁₃O₁₂	详情	详情
(XIX)	46757	benzyl (5S,8S,11R,14S,17S)-17-amino-5-[[(2S)-2-([[(1R)-2-amino-1-methyl-2-oxoethyl]amino]carbonyl)pyrrolidinyl]carbonyl]-11-(4-[[(tert-butylamino)carbonyl]amino]benzyl)-14-[4-([[(4R)-2,6-dioxohexahydro-4-pyrimidinyl]carbonyl]amino)benzyl]-8-isobutyl-7,10,13,16-tetraoxo-20-phenyl-19-oxa-6,9,12,15-tetraazaicos-1-yl(isopropyl)carbamate		C₆₉H₉₄N₁₄O₁₄	详情	详情

合成路线2

该中间体在本合成路线中的序号：(XVI)

Alternatively, after coupling of the peptide resin (XIII) with alpha-Boc-L-4-(Fmoc-amino)phenylalanine (XIV), the Fmoc protecting group was not removed, yielding resin (XXVI). Subsequent coupling cycles with amino acids (XVIII), (XX), (XXII) and (XXIV) as above finally produced resin (XXVII). The Fmoc group was then deprotected by treatment with piperidine, and the resulting aniline was acylated with L-hydroorotic acid (XVI) to provide resin (XXVIII), which was finally cleaved and deprotected by treatment with HF.

参考文献中间体

合成目标

【1】 Stalewski, J.; Galyean, R.; Jiang, G.; et al.; GnRH antagonists: A new generation of long acting analogues incorporating p-ureido-phenylalanines at positions 5 and 6. J Med Chem 2001, 44, 3, 453.
【2】 Jiang, G.; Semple, G. (Ferring BV Group Holding); GnRH antagonists being modified in positions 5 and 6. WO 9846634 .

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(XIII)	46749	benzyl (5S)-5-[((2S)-2-[[(2R)-2-amino-3-(4-[[(tert-butylamino)carbonyl]amino]phenyl)propanoyl]amino]-4-methylpentanoyl)amino]-6-[(2S)-2-([[(1R)-2-amino-1-methyl-2-oxoethyl]amino]carbonyl)pyrrolidinyl]-6-oxohexyl(isopropyl)carbamate		C₄₅H₆₉N₉O₈	详情	详情
(XIV)	46753	(2S)-3-(4-aminophenyl)-2-[(tert-butoxycarbonyl)amino]propionic acid	55533-24-9	C₁₄H₂₀N₂O₄	详情	详情
(XVI)	46755	(4R)-2,6-dioxohexahydro-4-pyrimidinecarboxylic acid		C₅H₆N₂O₄	详情	详情
(XXVI)	46761	9H-fluoren-9-ylmethyl 4-[(2S,5R,8S,11S)-11-[[(2S)-2-([[(1R)-2-amino-1-methyl-2-oxoethyl]amino]carbonyl)pyrrolidinyl]carbonyl]-2-[(tert-butoxycarbonyl)amino]-5-(4-[[(tert-butylamino)carbonyl]amino]benzyl)-8-isobutyl-16-isopropyl-3,6,9,17-tetraoxo-19-phenyl-18-oxa-4,7,10,16-tetraazanonadec-1-yl]phenylcarbamate		C₇₄H₉₇N₁₁O₁₃	详情	详情
(XXVII)	46762	benzyl (5S,8S,11R,14S,17S,20R,23R,26R)-5-[[(2S)-2-([[(1R)-2-amino-1-methyl-2-oxoethyl]amino]carbonyl)pyrrolidinyl]carbonyl]-17-[(benzyloxy)methyl]-11-(4-[[(tert-butylamino)carbonyl]amino]benzyl)-23-(4-chlorobenzyl)-14-(4-[[(9H-fluoren-9-ylmethoxy)ca		C₁₁₁H₁₂₉ClN₁₆O₁₇	详情	详情
(XXVIII)	46763	benzyl (5S,8S,11R,14S,17S,20R,23R,26R)-5-[[(2S)-2-([[(1R)-2-amino-1-methyl-2-oxoethyl]amino]carbonyl)pyrrolidinyl]carbonyl]-17-[(benzyloxy)methyl]-11-(4-[[(tert-butylamino)carbonyl]amino]benzyl)-23-(4-chlorobenzyl)-14-[4-([[(4R)-2,6-dioxohexahydro-4		C₁₀₁H₁₂₃ClN₁₈O₁₈	详情	详情

Extended Information