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【结 构 式】 
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【药物名称】Ceftaroline, T-91825, PPI-0903M 【化学名称】(6R,7R)-7-[(Z)-2-(5-Amino-1,2,4-thiadiazol-3-yl)-2-(ethoxyimino)acetamido]-3-[4-(1-methylpyridinium-4-yl)thiazol-2-ylsulfanyl]-3-cephem-4-carboxylate 【CA登记号】189345-04-8 【 分 子 式 】C22H20N8O5S4 【 分 子 量 】604.7113 |
【开发单位】Takeda (Originator) 【药理作用】Antibiotics, ANTIINFECTIVE THERAPY, Cephalosporins |
合成路线1
The bromination of 4-acetylpyridine (I) with Br2 and HBr in acetic acid gives 4-bromoacetylpyridine (II), which is cyclized with ammonium dithiocarbamate (III) and NaOMe to yield the thiazole (IV). The condensation of the sodium salt (IV) with the cephalosporanic ester (V) in THF affords the adduct (VI), which is treated with methyl iodide to provide the pyridinium salt (VII). The deprotection of (VII) with PCl5 and pyridine gives the aminocephalosporanic derivative (VIII), which is treated with TFA and anisole, yielding the inner salt (IX). Finally, this compound is condensed with the acid chloride (X) by means of NaHCO3 in THF/water to afford the target cephalosporin.
| 【1】 Ishikawa, T.; Matsunaga, N.; Tawada, H.; et al.; TAK-599, a novel N-phosphono type prodrug of anti-MRSA cephalosporin T-91825: Synthesis, physicochemical and pharmacological properties. 42nd Intersci Conf Antimicrob Agents Chemother (Sept 27 2002, San Diego) 2002, Abst F-332. |
| 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) | 59510 | 4-Acetylpyridine; Methyl 4-pyridyl ketone | 1122-54-9 | C7H7NO | 详情 | 详情 |
| (II) | 61522 | 2-bromo-1-(4-pyridinyl)-1-ethanone | C7H6BrNO | 详情 | 详情 | |
| (III) | 61523 | amino(aminosulfanyl)thioxomethane | CH4N2S2 | 详情 | 详情 | |
| (IV) | 61524 | C8H5N2NaS2 | 详情 | 详情 | ||
| (V) | 61525 | 4-methoxybenzyl (6R,7R)-7-[(ethoxycarbonyl)amino]-8-oxo-3-{[(trifluoromethyl)sulfonyl]oxy}-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate | C19H19F3N2O9S2 | 详情 | 详情 | |
| (VI) | 61526 | 4-methoxybenzyl (6R,7R)-7-[(ethoxycarbonyl)amino]-8-oxo-3-{[4-(4-pyridinyl)-1,3-thiazol-2-yl]sulfanyl}-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate | C26H24N4O6S3 | 详情 | 详情 | |
| (VII) | 61527 | 4-{2-[((6R,7R)-7-[(ethoxycarbonyl)amino]-2-{[(4-methoxybenzyl)oxy]carbonyl}-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-en-3-yl)sulfanyl]-1,3-thiazol-4-yl}-1-methylpyridinium iodide | C27H27IN4O6S3 | 详情 | 详情 | |
| (VIII) | 61528 | 4-{2-[((6R,7R)-7-amino-2-{[(4-methoxybenzyl)oxy]carbonyl}-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-en-3-yl)sulfanyl]-1,3-thiazol-4-yl}-1-methylpyridinium chloride | C24H23ClN4O4S3 | 详情 | 详情 | |
| (IX) | 61529 | (6R,7R)-7-amino-3-{[4-(1-methyl-4-pyridiniumyl)-1,3-thiazol-2-yl]sulfanyl}-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate | C16H14N4O3S3 | 详情 | 详情 | |
| (X) | 31455 | 2-(5-amino-1,2,4-thiadiazol-3-yl)-2-(ethoxyimino)acetyl chloride | C6H7ClN4O2S | 详情 | 详情 |