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【结 构 式】 
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【药物名称】CP-0467 【化学名称】7-[2-(5-Amino-1,2,4-thiadiazol-4-yl)-2(Z)-(methoxyimino)acetamido]-3-(benzothiazol-2-ylthio)-3-cephem-4-carboxylic acid sodium salt 【CA登记号】 【 分 子 式 】C19H14N7NaO5S4 【 分 子 量 】571.61313 |
【开发单位】Meiji Seika (Originator) 【药理作用】Cephalosporins |
合成路线1
The substitution of the triflate group of (I) by the sodium thiolate (II) provided a mixture of 3-cephem (III) and 2-cephem (IV) compounds. Without purification, treatment of the mixture with m-chloroperbenzoic acid gave the corresponding S-oxides, which were reduced with PCl3 to yield the 3-cephem (III). The phenylacetyl group was removed by treatment with PCl5 and pyridine, followed by hydrolysis with MeOH to afford amine (V). Acylation with acid (VI) in the presence of dicyclohexyl carbodiimide (DCC) and 1-hydroxybenzotriazole (HOBT) yielded amide (VII). Then, removal of the benzhydryl protecting group using trifluoroacetic acid and anisole, followed by treatment with aqueous NaHCO3 provided the target cephalosporin.
| 【1】 Tsushima, M.; Iwamatsu, K.; Tamura, A.; Shibahara, S.; Novel cephalosporin derivatives possessing a bicyclic heterocycle at the 3-position. Part I: Synthesis and biological activities of 3-(benzothiazol-2-yl)thiocephalosporin derivatives, CP0467 and related compounds. Bioorg Med Chem 1998, 6, 7, 1009. |
| 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) | 18209 | benzhydryl 8-oxo-7-[(2-phenylacetyl)amino]-3-[[(trifluoromethyl)sulfonyl]oxy]-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate | C29H23F3N2O7S2 | 详情 | 详情 | |
| (II) | 18210 | Benzothiazole-2-thiol sodium salt | C7H4NNaS2 | 详情 | 详情 | |
| (III) | 18211 | benzhydryl 3-(1,3-benzothiazol-2-ylsulfanyl)-8-oxo-7-[(2-phenylacetyl)amino]-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate | C35H27N3O4S3 | 详情 | 详情 | |
| (IV) | 18212 | benzhydryl 3-(1,3-benzothiazol-2-ylsulfanyl)-8-oxo-7-[(2-phenylacetyl)amino]-5-thia-1-azabicyclo[4.2.0]oct-3-ene-2-carboxylate | C35H27N3O4S3 | 详情 | 详情 | |
| (V) | 18213 | benzhydryl 7-amino-3-(1,3-benzothiazol-2-ylsulfanyl)-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate | C27H21N3O3S3 | 详情 | 详情 | |
| (VI) | 11757 | 2-(5-Amino-1,2,4-thiadiazol-3-yl)-2-(methoxyimino)acetic acid | C5H6N4O3S | 详情 | 详情 | |
| (VII) | 18215 | benzhydryl 7-[[2-(5-amino-1,2,4-thiadiazol-3-yl)-2-(methoxyimino)acetyl]amino]-3-(1,3-benzothiazol-2-ylsulfanyl)-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate | C32H25N7O5S4 | 详情 | 详情 |