(2S,4S)-4-[(4-methoxybenzyl)sulfanyl]-1-[[(4-nitrobenzyl)oxy]carbonyl]-2-pyrrolidinecarboxylic acid -Drug Synthesis Database

【结构式】

【分子编号】26814

【品名】(2S,4S)-4-[(4-methoxybenzyl)sulfanyl]-1-[[(4-nitrobenzyl)oxy]carbonyl]-2-pyrrolidinecarboxylic acid

【CA登记号】

【分子式】C₂₁H₂₂N₂O₇S

【分子量】446.48096

【元素组成】C 56.49% H 4.97% N 6.27% O 25.08% S 7.18%

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：(I)

Mercaptoproline derivative (I) was condensed with N-(carbamoylmethyl)homopiperazine (II) via activation with carbonyl diimidazole to afford amide (III). The 4-methoxybenzyl group of (III) was then removed with trifluoromethanesulfonic acid in the presence of anisole and trifluoroacetic acid, and the resulting mercaptan (IV) was condensed with carbapenem phosphate (VI), (prepared from ketone (V) and diphenylphosphorochloridate), to afford thioether (VII). N-Methylation of (VII) was carried out using methyl fluorosulfonate to yield quaternary ammonium salt (VIII). Finally, the 4-nitrobenzyl ester and carbamate groups of (VIII) were eliminated by hydrogenation in the presence of Pd/C, and the target product was isolated by ion-exchange chromatography.

参考文献中间体

合成目标

【1】 Ishikawa, K.; Kojima, K.; Miyauchi, M.; Endo, R.; Yasuda H; Kawamoto I.; Synthesis and structure-activity relationships of 1beta-methylcarbapenems with quaternary ammonium side chains. J Antibiot 1998, 51, 8, 757.
【2】 Kawamoto, I.; Miyauchi, M.; Nakayama, E.; Endo, R.; Ohya, S.; Utsui, Y. (Sankyo Co., Ltd.); Carbapenem derivs. having antibiotic activity, their preparation and their use. EP 0443883; JP 1992211083; US 5310735 .

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)	26814	(2S,4S)-4-[(4-methoxybenzyl)sulfanyl]-1-[[(4-nitrobenzyl)oxy]carbonyl]-2-pyrrolidinecarboxylic acid		C₂₁H₂₂N₂O₇S	详情	详情
(II)	26815	2-(1,4-diazepan-1-yl)acetamide		C₇H₁₅N₃O	详情	详情
(III)	26816	4-nitrobenzyl (2S,4S)-2-[[4-(2-amino-2-oxoethyl)-1,4-diazepan-1-yl]carbonyl]-4-[(4-methoxybenzyl)sulfanyl]-1-pyrrolidinecarboxylate		C₂₈H₃₅N₅O₇S	详情	详情
(IV)	26817	4-nitrobenzyl (2S,4S)-2-[[4-(2-amino-2-oxoethyl)-1,4-diazepan-1-yl]carbonyl]-4-sulfanyl-1-pyrrolidinecarboxylate		C₂₀H₂₇N₅O₆S	详情	详情
(V)	22575	4-nitrobenzyl (2R,5R,6S)-6-[(1R)-1-hydroxyethyl]-4-methyl-3,7-dioxo-1-azabicyclo[3.2.0]heptane-2-carboxylate		C₁₇H₁₈N₂O₇	详情	详情
(VI)	13224	4-nitrobenzyl (4R,5R,6S)-3-[(diphenoxyphosphoryl)oxy]-6-[(1R)-1-hydroxyethyl]-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylate	90776-59-3	C₂₉H₂₇N₂O₁₀P	详情	详情
(VII)	26818	4-nitrobenzyl (4R,5S,6S)-3-[((3S,5S)-5-[[4-(2-amino-2-oxoethyl)-1,4-diazepan-1-yl]carbonyl]-1-[[(4-nitrobenzyl)oxy]carbonyl]pyrrolidinyl)sulfanyl]-6-[(1R)-1-hydroxyethyl]-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylate		C₃₇H₄₃N₇O₁₂S	详情	详情
(VIII)	26819	(1R,5S,6S)-2-[5(S)-[4-(carbamoylmethyl)-4-methylperhydro-1,4-diazepinium-1-ylcarbonyl]-1-(4-nitrobenzyloxycarbonyl)pyrrolidin-3-(S)-ylsulfanyl]-6-(1(R)-hydroxyethyl)-1-methyl-1-carba-2-penem-3-carboxylic acid 4-nitrobenzyl ester fluorosulfonate; (1R,5S,6S)-2-[5(S)-[4-(carbamoylmethyl)-4-methylperhydro-1,4-diazepinium-1-ylcarbonyl]-1-(4-nitrobenzyloxycarbonyl)pyrrolidin-3-(S)-ylsulfanyl]-6-(1(R)-hydroxyethyl)-1-methyl-1-carba-2-penem-3-carboxylic acid 4-nitrobenzyl ester fluorosulfonate		C₃₈H₄₆FN₇O₁₅S₂	详情	详情

Extended Information