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【结 构 式】 
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【药物名称】 【化学名称】7-[2-(2-Aminothiazolyl-4-yl)-2(Z)-(methoxyimino)acetamido]-3-(3-chloroisoxazol-5-ylvinyl)-3-cephem-4-carboxylic acid sodium salt 【CA登记号】 【 分 子 式 】C18H14ClN6NaO6S2 【 分 子 量 】532.91968 |
【开发单位】Korea Inst. Sci. Technol. (Originator) 【药理作用】Antibiotics, ANTIINFECTIVE THERAPY, Cephalosporins |
合成路线1
Trityl protected 2-(2-aminothiazol-4-yl)-2-(methoxy)iminoacetic acid (I) was coupled to 7-amino-3-(chloromethyl)cephalosporanic acid p-methoxybenzyl ester (II) using POCl3 and pyridine to give amide (III). This was converted to phosphonium salt (IV) upon treatment with triphenylphosphine and NaI. Subsequent Wittig reaction of (IV) with 3-chloroisoxazole-5-carbaldehyde (V) produced the corresponding vinyl isoxazole as a mixture of geometrical isomers, from which the major trans isomer (VI) was separated by flash column chromatography. Finally, deprotection of both trityl and p-methoxybenzyl groups of (VI) by means of trifluoroacetic acid afforded the title compound, which was isolated as the sodium salt.
| 【1】 Cho, Y.S.; Pae, A.N.; Cha, J.H.; Choi, K.I.; Chang, M.H.; Koh, H.Y.; Studies on novel 3-isoxazolylvinylcephalosporins: I. Synthesis and biological activity of 7-[2-(2-aminothiazol-4-yl)-2-(alkoxy)iminoacetamido] derivatives. J Antibiot 1998, 51, 12, 1117. |
| 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) | 25058 | 2-(methoxyimino)-2-[2-(tritylamino)-1,3-thiazol-4-yl]acetic acid | 64485-90-1 | C25H21N3O3S | 详情 | 详情 |
| (II) | 26869 | 4-methoxybenzyl 7-amino-3-(chloromethyl)-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate | C16H17ClN2O4S | 详情 | 详情 | |
| (III) | 25062 | 4-methoxybenzyl 3-(chloromethyl)-7-([2-(methoxyimino)-2-[2-(tritylamino)-1,3-thiazol-4-yl]acetyl]amino)-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate | C41H36ClN5O6S2 | 详情 | 详情 | |
| (IV) | 25065 | [[2-[[(4-methoxybenzyl)oxy]carbonyl]-7-([2-(methoxyimino)-2-[2-(tritylamino)-1,3-thiazol-4-yl]acetyl]amino)-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-en-3-yl]methyl](triphenyl)phosphonium iodide | C59H51IN5O6PS2 | 详情 | 详情 | |
| (V) | 25067 | 3-chloro-5-isoxazolecarbaldehyde | C4H2ClNO2 | 详情 | 详情 | |
| (VI) | 26870 | 4-methoxybenzyl 3-[(E)-2-(3-chloro-5-isoxazolyl)ethenyl]-7-([2-(methoxyimino)-2-[2-(tritylamino)-1,3-thiazol-4-yl]acetyl]amino)-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate | C45H37ClN6O7S2 | 详情 | 详情 |