benzhydryl (6R,7R)-7-amino-3-[[(1-methyl-1H-1,2,3,4-tetraazol-5-yl)sulfanyl]methyl]-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate -Drug Synthesis Database

【结构式】

【分子编号】28910

【品名】benzhydryl (6R,7R)-7-amino-3-[[(1-methyl-1H-1,2,3,4-tetraazol-5-yl)sulfanyl]methyl]-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate

【CA登记号】

【分子式】C₂₃H₂₂N₆O₃S₂

【分子量】494.59832

【元素组成】C 55.85% H 4.48% N 16.99% O 9.7% S 12.97%

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：(IV)

The condensation of 4-ethyl-2,3-dioxo-1-piperazinecarbonyl chloride (I) with threonine (II) in methylene chloride gives alpha-(4-ethyl-2,3-dioxo-1-piperazinecarboxamido)-beta-hydroxybutyric acid (III), which is then condensed with diphenylmethyl 7-beta-amino-3-[(1-methyltetrazol-5-yl)thiometnyl)-Delta3-cephem-4-carboxylate (IV) by means of ethyl chloroformate and N-methyl morpholine yielding diphenylmethyl 7-beta-[alpha-(4-ethyl-2,3-dioxo-1-piperazi-necarboxamido)-beta-hydroxybutyramido]-3-(11-methyltetrazol-5-yl)thiomethyl]-Delta3-cephem-4-carboxylate (V). The methoxylation of (V) with lithium methoxide-methylene chloride THF affords diphenyl methyl 7-beta-[alpha-(4-ethyl-2,3-dioxo-1-piperazinecarboxamido)-beta-hydroxybutyramido]-7-alpha-methoxy-3-[(1-methyltetrazol-5-yl)thiamethyl-Delta3-cephem-4-carboxylate (VI), which is finally hydrolyzed with trifluoroacetic acid, and treated with NaHCO3 to obtain the sodium salt.

参考文献中间体

合成目标

【1】 Saikawa, I.; et al. (Toyama Chemical Co., Ltd.); Novel 7alpha-methoxycephalosporins and process for producing the same. FR 2455051; GB 2048241; JP 80141.491; JP 8125188; US 4263292 .
【2】 Burnie, J.; Serradell, M.N.; Castaner, J.; Cefbuperazone Sodium. Drugs Fut 1985, 10, 1, 14.

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)	24305	4-ethyl-2,3-dioxo-1-piperazinecarbonyl chloride	59703-00-3	C₇H₉ClN₂O₃	详情	详情
(II)	28908	L-Threonine; (2R,3S)-2-amino-3-hydroxybutyric acid	632-20-2	C₄H₉NO₃	详情	详情
(III)	28909	(2R,3S)-2-[[(4-ethyl-2,3-dioxo-1-piperazinyl)carbonyl]amino]-3-hydroxybutyric acid		C₁₁H₁₇N₃O₆	详情	详情
(IV)	28910	benzhydryl (6R,7R)-7-amino-3-[[(1-methyl-1H-1,2,3,4-tetraazol-5-yl)sulfanyl]methyl]-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate		C₂₃H₂₂N₆O₃S₂	详情	详情
(V)	28911	benzhydryl (6R,7R)-7-[((2R,3S)-2-[[(4-ethyl-2,3-dioxo-1-piperazinyl)carbonyl]amino]-3-hydroxybutanoyl)amino]-3-[[(1-methyl-1H-1,2,3,4-tetraazol-5-yl)sulfanyl]methyl]-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate		C₃₄H₃₇N₉O₈S₂	详情	详情
(VI)	28912	benzhydryl (6R,7S)-7-[((2R,3S)-2-[[(4-ethyl-2,3-dioxo-1-piperazinyl)carbonyl]amino]-3-hydroxybutanoyl)amino]-7-methoxy-3-[[(1-methyl-1H-1,2,3,4-tetraazol-5-yl)sulfanyl]methyl]-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate		C₃₅H₃₉N₉O₉S₂	详情	详情

Extended Information