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【结 构 式】 
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【药物名称】CM-40874 【化学名称】7-[2-(2-Amino-4-thiazolyl)-2-[(2-carboxy-2-propoxy)imino]acetamido]-3-[[(1-allylpyridinium-2-yl)thio]methyl]-3-cephem-4-carboxylic acid 1-oxide bromide 【CA登记号】87286-08-6 【 分 子 式 】C25H27BrN6O8S3 【 分 子 量 】715.62534 |
【开发单位】Sanofi-synthélabo (Originator) 【药理作用】Antibiotics, ANTIINFECTIVE THERAPY, Cephalosporins |
合成路线1
The condensation of 7-amino-3-bromomethyl-3-cephem-4-carboxylic acid tert-butyl ester 1-oxide (I) with 2-(2-tritylamino-4-thiazolyl)-2-[2-(tert-butoxycarbonyl)-2-propyloxyimino]acetic acid (II) by means of dicyclohexylcarbodiimide in CH2Cl2 gives the corresponding amide (III), which is treated with N-allyl-pyridine-2-thione (IV) in dimethylacetamide yielding the pyridinium salt (V). Finally, this compound is deprotected by a treatment with HCl in formic acid. The thione (IV) is prepared as follows: The reaction of 2-bromopyridine (VI) with allyl bromide (VII) in acetone gives N-allyl-2-bromopyridinium bromide (VIII), which is then treated with potassium hydrosulfide in water.
| 【1】 Labeeuw, B.; Salhi, A. (Sanofi-Synthelabo); Derivatives of pyridinium thiomethyl cephalosporins. EP 0088853; FR 2516515; JP 58090590; US 4593022 . |
| 【2】 Serradell, M.N.; Matthews, R.; Castaner, J.; Burnie, J.; CM-40874. Drugs Fut 1985, 10, 3, 193. |
| 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) | 29048 | tert-butyl 7-amino-3-(bromomethyl)-5,8-dioxo-5lambda(4)-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate | C12H17BrN2O4S | 详情 | 详情 | |
| (II) | 29047 | 2-[[2-(tert-butoxy)-1,1-dimethyl-2-oxoethoxy]imino]-2-[2-(tritylamino)-1,3-thiazol-4-yl]acetic acid | C32H33N3O5S | 详情 | 详情 | |
| (III) | 29049 | tert-butyl 3-(bromomethyl)-7-([2-[[2-(tert-butoxy)-1,1-dimethyl-2-oxoethoxy]imino]-2-[2-(tritylamino)-1,3-thiazol-4-yl]acetyl]amino)-5,8-dioxo-5lambda(4)-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate | C44H48BrN5O8S2 | 详情 | 详情 | |
| (IV) | 29050 | 1-allyl-2(1H)-pyridinethione | C8H9NS | 详情 | 详情 | |
| (V) | 29051 | 1-allyl-2-([[2-(tert-butoxycarbonyl)-7-([2-[[2-(tert-butoxy)-1,1-dimethyl-2-oxoethoxy]imino]-2-[2-(tritylamino)-1,3-thiazol-4-yl]acetyl]amino)-5,8-dioxo-5lambda(4)-thia-1-azabicyclo[4.2.0]oct-2-en-3-yl]methyl]sulfanyl)pyridinium bromide | C52H57BrN6O8S3 | 详情 | 详情 | |
| (VI) | 29052 | 2-Bromopyridine；α-bromopyridine;α-bromoazine | 109-04-6 | C5H4BrN | 详情 | 详情 |
| (VII) | 11463 | 3-Bromo-1-propene; 3-Bromopropene；allyl bromide | 106-95-6 | C3H5Br | 详情 | 详情 |
| (VIII) | 29053 | 1-allyl-2-bromopyridinium bromide | C8H9Br2N | 详情 | 详情 |