-Drug Synthesis Database

【结构式】

【药物名称】

【化学名称】7-[2-(2-Aminothiazol-4-yl)-2(Z)-[1(S)-carboxyethoxyimino]acetamido]-3-(5-methylthiazolo[4,5-c]pyridinium-2-ylsulfanylmethyl)-3-cephem-4-carboxylate sodium salt

【CA登记号】

【分子式】C₂₃H₂₀N₇NaO₇S₄

【分子量】657.70435

【开发单位】Meiji Seika (Originator)

【药理作用】Antibacterial Drugs, ANTIINFECTIVE THERAPY, Cephalosporins

合成路线1 合成路线2

合成路线1

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

【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

Pyridinium salt (VII) was followed by deprotection of the N-trityl and the benzyl ester groups in trifluoroacetic acid containing anisole, to furnish acid (VIII) as the inner salt with the pyridinium group. The remaining carboxylic acid group of (VIII) was finally converted to the sodium salt upon treatment with aqueous NaHCO3, and the target compound was purified by Diaion HP-20 column chromatography.

参考文献中间体

【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	CAS号	分子式	供应商	用于合成
(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
(VIII)	21634	(7R)-7-[[2-(2-amino-1,3-thiazol-4-yl)-2-([[(1S)-1-carboxyethyl]oxy]imino)acetyl]amino]-3-[[(5-methyl[1,3]thiazolo[4,5-c]pyridin-5-ium-2-yl)sulfanyl]methyl]-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate		C₂₃H₂₁N₇O₇S₄	详情	详情

Extended Information