- 【药物名称】Cefotaxime sodium, HR-756, Claforan
- 【化学名】(6R,7R)-3-(Acetoxymethyl)-7-[2-(2-aminothiazol-4-yl)-2-(methoxyimino)acetamido]-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid sodium salt
- 【CAS登记号】64485-93-4, 63527-52-6 (free base)
- 【结构式】
- 【分子式】C16-H16-N5-O7-S2.Na
- 【分子量】477.4524
- 【原研厂家】Aventis Pharma (Originator), Abbott (Licensee)
- 【作用类别】Antibacterial Drugs, ANTIINFECTIVE THERAPY, Cephalosporins
- 【研发状态】Launched-1980
- 【合成情况】
- 〖来源〗Drugs Fut
- 〖合成路线〗
- 〖标题〗HR-756
- 〖合成方法〗The protection of the amino group of ethyl 2-(2-amino-4-thiazolyl)-2-methoxyiminoacetate (I) with trityl chloride (B) by means of triethylamine in CH2Cl2 gives ethyl 2-(2-tritylamino-4-thiazolyl)-2-methoxyimino acetate (II), which is hydrolyzed to the corresponding acid (III) with NaOH in refluxing dioxane-water. The condensation of (III) with 7-aminocephalosporanic acid (IV) by means of dicyclohexylcarbodiimide in CH2Cl2 containing triethylamine affords 7-(2-(2-tritylamino-4-thiazolyl)-2-methoxyiminoacetamido]cephalosporanic acid (V). The elimination of the trityl group is performed with hot 55% formic acid yielding the corresponding free acid, which is finally treated with NaHCO3 in water.
- 〖作者〗Neuman, M.; Castaer, J.
- 〖参考〗Neuman, M.; Castaer, J.; HR-756. Drugs Fut 1978, 3, 10, 749
- 〖出处〗Drugs Fut1978,3,(10):749
- 〖备注〗Synthesis of Cefotaxime sodium (EN:070045): The protection of the amino group of ethyl 2-(2-amino-4-thiazolyl)-2-methoxyiminoacetate (I) with trityl chloride (B) by means of triethylamine in CH2Cl2 gives ethyl 2-(2-tritylamino-4-thiazolyl)-2-methoxyimino acetate (II), which is hydrolyzed to the correspon-ing acid (III) with NaOH in refluxing dioxane-water. The condensation of (III) with 7-aminocephalosporanic acid (IV) by means of dicyclohexylcarbodiimide in CH2Cl2 containing triethylamine affords 7-(2-(2-tritylamino-4-thiazolyl)-2-methoxyiminoacetamido]cephalosporanic acid (V). The elimination of the trityl group is performed with hot 55% formic acid yielding the corresponding free acid, which is finally treated with NaHCO3 in water. (Scheme 07004501a) The starting product (I) can be obtained in two different ways (Scheme 07004501a): 1) The methylation of ethyl gamma-chloro-alpha-oxyiminoacetylacetate (VI) with diazomethane in CH2Cl2 gives ethyl gamma-chloro-alpha-methoxyiminoacetylacetate (VII), which is finally treated with thiourea (A) in dry ethanol. 2) The methylation of ethyl alpha-hydroxyiminoacetylacetate (VIII) with dimethyl sulfate by means of K2CO3 in acetone gives ethyl alpha-methoxyiminoacetylacetate (IX), which is brominated with Br2 in CH2Cl2 yielding ethyl 4-bromo-2-methoxyiminoacetylacetate (X). Finally this compound is treated with thiourea (A) as before (1). Manufacturer Lab. Roussel-Hoechst (France-Germany). Reference 1. Roussel Uclaf; BE 850662.
- 〖来源〗BE 0850662; ES 455089; ES 466539; GB 1580621; GB 1580623; JP 52102293; JP 5247013
- 〖合成路线〗
- 〖标题〗Oxime derivatives of 7-aminothiazolylacetamidocephalosporanic acid processes for preparing them and pharmaceutical compositions incorporating them
- 〖合成方法〗The protection of the amino group of ethyl 2-(2-amino-4-thiazolyl)-2-methoxyiminoacetate (I) with trityl chloride (B) by means of triethylamine in CH2Cl2 gives ethyl 2-(2-tritylamino-4-thiazolyl)-2-methoxyimino acetate (II), which is hydrolyzed to the corresponding acid (III) with NaOH in refluxing dioxane-water. The condensation of (III) with 7-aminocephalosporanic acid (IV) by means of dicyclohexylcarbodiimide in CH2Cl2 containing triethylamine affords 7-(2-(2-tritylamino-4-thiazolyl)-2-methoxyiminoacetamido]cephalosporanic acid (V). The elimination of the trityl group is performed with hot 55% formic acid yielding the corresponding free acid, which is finally treated with NaHCO3 in water.
- 〖作者〗Heymes, R.; Lutz, A. (Aventis Pharma SA)
- 〖参考〗Heymes, R.; Lutz, A. (Aventis Pharma SA); Oxime derivatives of 7-aminothiazolylacetamidocephalosporanic acid processes for preparing them and pharmaceutical compositions incorporating them. BE 0850662; ES 455089; ES 466539; GB 1580621; GB 1580623; JP 5210 ???d?^ f
- 〖出处〗BE 0850662; ES 455089; ES 466539; GB 1580621; GB 1580623; JP 52102293; JP 5247013,,():
- 〖备注〗
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