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【结 构 式】 
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【药物名称】Cefpirome, HR-810, Cefrom(sulfate), Broact(sulfate), Keiten(sulfate) 【化学名称】1-[[(6R,7R)-7-[2-(2-Amino-4-thiazolyl)glyoxylamido]-2-carboxy-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-en-3-yl]methyl]-6,7-dihydro-5H-1-pyrindinium hydroxide,inner salt,7(2)-(Z)-(O-methyloxime) 【CA登记号】84957-29-9, 98753-19-6 (monosulfate) 【 分 子 式 】C22H22N6O5S2 【 分 子 量 】514.58584 |
【开发单位】Aventis Pharma (Originator), Fujisawa (Licensee), Shionogi (Licensee) 【药理作用】Antibacterial Drugs, ANTIINFECTIVE THERAPY, Cephalosporins |
合成路线1
The protection of 7-aminocephalosporanic acid (I) with di-tert-butyl dicarbonate gives 7-(tert-butoxycarbonylamino)cephalosporanic acid (II), which is condensed with 2,3-cyclopentenopyridine (III) by means of KI and NaHCO3 in hot water affording 7-(tert-butoxycarbonylamino)-3-[(2,3-cyclopenteno-1-pyridinium)methyl]ceph-3-em-4-carboxylate (IV). Deprotection of (IV) with trifluoroacetic acid anisole gives 7-amino-3-[(2,3-cyclopenteno-1-pyridinium)methyl]ceph-3-em-4-carboxylate (V), which is finally condensed with 2-(2-aminothiazol-4-yl)-2-syn-methoxyiminoacetic acid (VI) by means of phosgene in toluene.
| 【1】 Klesel, N.; Seibert, G.; Lattrell, R.; Wieduwilt, M.; Durckheimer, W.; Kirrstetter, R.; HR-810, a new parenteral cephalosporin. I. Chemistry and physical properties. Int Con Chemother 1983, PS 4.2/11-1. |
| 【2】 Klesel, N.; Dürckheimer, W.; Blumbach, J.; Lattrell, R.; Scheunemann, K.H.; Wieduwilt, M.; Schwab, W.; Ross, B.C.; Limbert, M.; Winkler, I.; Seibert, G.; Mencke, B.; Kirrstetter, R.; Seeger, K.; Schrinner, E.; Fleischmann, K.; HR-810, a new parenteral cephalosporin with a broad antibacterial spectrum. Arzneim-Forsch Drug Res 1983, 33, 8, 1084-1086. |
| 【3】 Lattrell, R.; Wieduwilt, M.; Duerckheimer, W.; Blumbach, J.; Seeger, K. (Aventis SA); Cephalosporin derivatives. EP 0064740; FR 2511682; FR 2515654; GB 2098216; JP 57192394; US 5071979 . |
| 【4】 Castaner, J.; Serradell, M.N.; Cefpirome. Drugs Fut 1984, 9, 4, 252. |
| 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) | 22747 | (6R,7R)-3-[(acetoxy)methyl]-7-amino-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid | C10H12N2O5S | 详情 | 详情 | |
| (II) | 30507 | (6R,7R)-3-[(acetoxy)methyl]-7-[(tert-butoxycarbonyl)amino]-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid | C15H20N2O7S | 详情 | 详情 | |
| (III) | 30508 | 6,7-dihydro-5H-cyclopenta[b]pyridine | 533-37-9 | C8H9N | 详情 | 详情 |
| (IV) | 30509 | (6R,7R)-7-[(tert-butoxycarbonyl)amino]-3-(6,7-dihydro-5H-cyclopenta[b]pyridinium-1-ylmethyl)-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate | C21H25N3O5S | 详情 | 详情 | |
| (V) | 30510 | (6R,7R)-7-amino-3-(6,7-dihydro-5H-cyclopenta[b]pyridinium-1-ylmethyl)-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate | C16H17N3O3S | 详情 | 详情 | |
| (VI) | 24737 | 2-(2-amino-1,3-thiazol-4-yl)-2-(methoxyimino)acetic acid | 65872-41-5 | C6H7N3O3S | 详情 | 详情 |
合成路线2
By condensation of (III) with 7-[2-syn-methoxyimino-2-(2-aminothiazo)-4-yl(acetamido]cephalosporanic acid (VII) with KI and NaHCO3.
| 【1】 Klesel, N.; Dürckheimer, W.; Blumbach, J.; Lattrell, R.; Scheunemann, K.H.; Wieduwilt, M.; Schwab, W.; Ross, B.C.; Limbert, M.; Winkler, I.; Seibert, G.; Mencke, B.; Kirrstetter, R.; Seeger, K.; Schrinner, E.; Fleischmann, K.; HR-810, a new parenteral cephalosporin with a broad antibacterial spectrum. Arzneim-Forsch Drug Res 1983, 33, 8, 1084-1086. |
| 【2】 Klesel, N.; Seibert, G.; Lattrell, R.; Wieduwilt, M.; Durckheimer, W.; Kirrstetter, R.; HR-810, a new parenteral cephalosporin. I. Chemistry and physical properties. Int Con Chemother 1983, PS 4.2/11-1. |
| 【3】 Lattrell, R.; Wieduwilt, M.; Duerckheimer, W.; Blumbach, J.; Seeger, K. (Aventis SA); Cephalosporin derivatives. EP 0064740; FR 2511682; FR 2515654; GB 2098216; JP 57192394; US 5071979 . |
| 【4】 Castaner, J.; Serradell, M.N.; Cefpirome. Drugs Fut 1984, 9, 4, 252. |