|
【结 构 式】 
|
【药物名称】Cefbuperazone sodium, T 1982, BMY-25182, Tomiporan, Keiperazon 【化学名称】(6R,7S)-7-[(2R,3S)-2-(4-Ethyl-2,3-dioxo-1-piperazinecarboxamido)-3-hydroxybutyramido]-7-methoxy-3-[[(1-methyl-1H-tetrazol-5-yl)thio]methl]-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid sodium salt 【CA登记号】76648-01-6, 76610-84-9 (free acid) 【 分 子 式 】C22H28N9NaO9S2 【 分 子 量 】649.64116 |
【开发单位】Bristol-Myers Squibb (Originator), Kaken (Originator), Toyama (Originator) 【药理作用】Antibacterial Drugs, ANTIINFECTIVE THERAPY, Cephalosporins |
合成路线1
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.
| 【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 |