4-methoxybenzyl (7R)-7-amino-3-(chloromethyl)-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate -Drug Synthesis Database

【结构式】

【分子编号】21627

【品名】4-methoxybenzyl (7R)-7-amino-3-(chloromethyl)-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate

【CA登记号】

【分子式】C₁₆H₁₇ClN₂O₄S

【分子量】368.84076

【元素组成】C 52.1% H 4.65% Cl 9.61% N 7.6% O 17.35% S 8.69%

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：(II)

Amino cephem compound (II) was condensed with acid (I) using phosphoryl chloride and pyridine to yield amide (III). After conversion of the chloromethyl group of (III) into the correspondig iodide (IV) upon treatment with NaI in acetone, displacement of the halogen atom with 2-mercaptothiazolo[4,5-c]pyridine (V) in DMF provided sulfide (VI). Quaternization of the pyridine nitrogen atom of (VI) with CH3I, to give pyridinium salt (VII).

参考文献中间体

合成目标

【1】 Tsushima, M.; Kano, Y.; Iwamatsu, K.; Tamura, A.; Umemura, E.; Shibahara, S.; Novel cephalosporin derivatives possessing a bicyclic heterocycle at the 3-position. Part II: Synthesis and antibacterial activity of 3-(5-methylthiazolo[4,5-c]pyridinium-2-yl)thiomethylcephalosporin derivatives and related compounds. Bioorg Med Chem 1998, 6, 9, 1641.

中间体序号	中间体编号	品名	分子式	供应商	用于合成
(I)	21626	2-([[(1S)-2-(benzhydryloxy)-1-methyl-2-oxoethyl]oxy]imino)-2-[2-(tritylamino)-1,3-thiazol-4-yl]acetic acid	C₄₀H₃₃N₃O₅S	详情	详情
(II)	21627	4-methoxybenzyl (7R)-7-amino-3-(chloromethyl)-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate	C₁₆H₁₇ClN₂O₄S	详情	详情
(III)	21628	4-methoxybenzyl (7R)-7-([2-([[(1S)-2-(benzhydryloxy)-1-methyl-2-oxoethyl]oxy]imino)-2-[2-(tritylamino)-1,3-thiazol-4-yl]acetyl]amino)-3-(chloromethyl)-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate	C₅₆H₄₈ClN₅O₈S₂	详情	详情
(IV)	21629	4-methoxybenzyl (7R)-7-([2-([[(1S)-2-(benzhydryloxy)-1-methyl-2-oxoethyl]oxy]imino)-2-[2-(tritylamino)-1,3-thiazol-4-yl]acetyl]amino)-3-(iodomethyl)-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate	C₅₆H₄₈IN₅O₈S₂	详情	详情
(V)	21630	[1,3]thiazolo[4,5-c]pyridine-2-thiol; [1,3]thiazolo[4,5-c]pyridin-2-ylhydrosulfide	C₆H₄N₂S₂	详情	详情
(VI)	21631	4-methoxybenzyl (7R)-7-([2-([[(1S)-2-(benzhydryloxy)-1-methyl-2-oxoethyl]oxy]imino)-2-[2-(tritylamino)-1,3-thiazol-4-yl]acetyl]amino)-8-oxo-3-[([1,3]thiazolo[4,5-c]pyridin-2-ylsulfanyl)methyl]-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate	C₆₂H₅₁N₇O₈S₄	详情	详情
(VII)	21632	2-[[((7R)-7-([2-([[(1S)-2-(benzhydryloxy)-1-methyl-2-oxoethyl]oxy]imino)-2-[2-(tritylamino)-1,3-thiazol-4-yl]acetyl]amino)-2-[[(4-methoxybenzyl)oxy]carbonyl]-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-en-3-yl)methyl]sulfanyl]-5-methyl[1,3]thiazolo[4,5-c]pyridin-5-ium iodide	C₆₃H₅₄IN₇O₈S₄	详情	详情

合成路线2

该中间体在本合成路线中的序号：(I)

The condensation of the aminocephem derivative (I) with the ethoxyiminoacetic acid (II) by means of POCl3 and NMM gives the corresponding amide (III), which is condensed with the imidazo pyridine (IV) by means of NaI or NaBr to yield the protected imidazopyridinium salt (V). Finally, this compound is deprotected by means of AlCl3 and anisole, TiCl4 and anisole or sulfuric and formic acids to afford the target cephem-carboxylate derivative.

参考文献中间体

合成目标

【1】 Itani, H.; Ishikura, K.; Yoshizawa, H.; et al.; S-3578, a new broad spectrum parenteral cephalosporin exhibiting potent activity against both methicillin-resistant Staphylococcus aureus (MRSA) and Pseudomonas aeruginosa synthesis and structure-activity relationships. J Antibiot 2002, 55, 11, 975.

中间体序号	中间体编号	品名	分子式	供应商	用于合成
(I)	21627	4-methoxybenzyl (7R)-7-amino-3-(chloromethyl)-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate	C₁₆H₁₇ClN₂O₄S	详情	详情
(II)	58660	tert-butyl 3-(2-amino-2-oxoethanimidoyl)-1,2,4-thiadiazol-5-ylcarbamate	C₁₁H₁₇N₅O₄S	详情	详情
(III)	54821	4-methoxybenzyl (7R)-7-{[2-{5-[(tert-butoxycarbonyl)amino]-1,2,4-thiadiazol-3-yl}-2-(ethoxyimino)acetyl]amino}-3-(chloromethyl)-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate	C₂₇H₃₁ClN₆O₈S₂	详情	详情
(IV)	54814	tert-butyl 3-(1H-imidazo[4,5-b]pyridin-1-yl)propyl(methyl)carbamate	C₁₅H₂₂N₄O₂	详情	详情
(V)	54822	4-[((7R)-7-{[2-{5-[(tert-butoxycarbonyl)amino]-1,2,4-thiadiazol-3-yl}-2-(ethoxyimino)acetyl]amino}-2-{[(4-methoxybenzyl)oxy]carbonyl}-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-en-3-yl)methyl]-1-{3-[(tert-butoxycarbonyl)(methyl)amino]propyl}-1H-imidazo[4,5-b]pyridin-4-ium	C₄₂H₅₃N₁₀O₁₀S₂	详情	详情

Extended Information