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【结 构 式】 
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【分子编号】44604 【品名】2-(2-amino-1,3-thiazol-4-yl)-2-(hydroxyimino)acetic acid 【CA登记号】 |
【 分 子 式 】C5H5N3O3S 【 分 子 量 】187.17912 【元素组成】C 32.08% H 2.69% N 22.45% O 25.64% S 17.13% |
合成路线1
该中间体在本合成路线中的序号：(IV)The synthesis of [14C]-labeled cefepime has been reported: The cyclization of [14C]-thiourea (I) with 4-bromo-2-(methoxyimino)-3-oxobutyric acid ethyl ester (II) in ethanol gives 2-(2-aminothiazol-4-yl)-2-(methoxyimino)acetic acid ethyl ester (III), which is hydrolyzed with NaOH in methanol to the corresponding free acid (IV). The esterification of (IV) with 1-hydroxybenzotriazole (V) by means of dicyclohexylcarbodiimide in THF affords the corresponding active ester (VI), which is condensed with 7-amino-3-(1-methylpyrrolidiniomethyl)-3-cephem-4-carboxylate (VII) by means of NaOH in THF-water and isolated as the sulfate salt (VIII). Finally, this compound is treated with triethylamine in N-methyl-2-pyrrolidone.
| 【1】 Swigor, J.E.; Standridge, R.T.; Synthesis of 7-[alpha-(2-amino-[2-14C]thiazol-4-yl)-alpha-(Z)-methoxyiminoacetamido]-3-(1-methylpyrrolidinio)methyl-3-cephem-4-carboxylate hydrochloride ([14C]cefepime hydrochloride). J Label Compd Radiopharm 1993, 33, 8, 759. |
| 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) | 10180 | Thiourea | 62-56-6 | CH4N2S | 详情 | 详情 |
| (I) | 44602 | thiourea | CH4N2S | 详情 | 详情 | |
| (II) | 10181 | ethyl 4-bromo-2-(methoxyimino)-3-oxobutanoate | 60845-87-6 | C7H10BrNO4 | 详情 | 详情 |
| (III) | 10182 | Ethyl 2-(2-aminothiazole-4-yl)-2-methoxyiminoacetate; ethyl 2-(2-amino-1,3-thiazol-4-yl)-2-(methoxyimino)acetate; 2-(2-Amino-4-thiazolyl)-2-methoxyiminoacetic acid ethyl ester | 64485-88-7 | C8H11N3O3S | 详情 | 详情 |
| (III) | 44603 | ethyl 2-(2-amino-1,3-thiazol-4-yl)-2-(methoxyimino)acetate | C8H11N3O3S | 详情 | 详情 | |
| (IV) | 10183 | (Z)-2-(2-aminothiazol-4-yl)-2-(hydroxyimino)acetic acid；2-(2-Amino-1,3-thiazol-4-yl)-2-(hydroxyimino)acetic acid | 66338-96-3 | C5H5N3O3S | 详情 | 详情 |
| (IV) | 44604 | 2-(2-amino-1,3-thiazol-4-yl)-2-(hydroxyimino)acetic acid | C5H5N3O3S | 详情 | 详情 | |
| (V) | 10184 | 1H-1,2,3-Benzotriazol-1-ol; 1-Hydroxybenzotriazole; 1H-Benzotriazol-1-ol; 1-Benzotriazolol | 2592-95-2 | C6H5N3O | 详情 | 详情 |
| (VI) | 10185 | 1-(2-Amino-1,3-thiazol-4-yl)-2-(1H-1,2,3-benzotriazol-1-yloxy)-2-oxo-1-ethanone oxime | C11H8N6O3S | 详情 | 详情 | |
| (VI) | 44605 | 1-(2-amino-1,3-thiazol-4-yl)-2-(1H-1,2,3-benzotriazol-1-yloxy)-2-oxo-1-ethanone oxime | C11H8N6O3S | 详情 | 详情 | |
| (VII) | 10186 | (6R,7R)-7-amino-3-[(1-methyltetrahydro-1H-pyrrolium-1-yl)methyl]-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate | C13H19N3O3S | 详情 | 详情 | |
| (VIII) | 10187 | 1-[((6R,7R)-7-[[2-(2-Amino-1,3-thiazol-4-yl)-2-(methoxyimino)acetyl]amino]-2-carboxy-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-en-3-yl)methyl]-1-methyltetrahydro-1H-pyrrolium | C19H25N6O5S2 | 详情 | 详情 | |
| (VIII) | 44606 | 1-[((6R,7R)-7-[[2-(2-amino-1,3-thiazol-4-yl)-2-(methoxyimino)acetyl]amino]-2-carboxy-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-en-3-yl)methyl]-1-methylpyrrolidinium | C19H25N6O5S2 | 详情 | 详情 |