Cefetamet pivoxil, Ro-15-8075, Globocef, Cefyl
头孢他美酯Chemical Name: (6R,7R)-7-[2-(2-Aminothiazol-4-yl)-(Z)-2-(methoxyimino)acetamido]-3-methyl-3-cephem-4-carboxylic acid pivaloyloxymethyl ester; [6R-[6alpha,7beta(Z)]]-7-[2-(2-Aminothiazol-4-yl)-2-(methoxyimino)acetamido]-3-methyl-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid (2,2-dimethyl-1-oxopropoxy)methyl ester
CAS No. 65243-33-6
项目整合开发状态: Launched-1992
项目研究机构: Roche (Originator), Takeda (Originator), Roche (Licensee)
合成路线:The methylation of ethyl 2-(hydroxyimino)-3-oxobutyrate (I) with dimethyl sulfate and Na2CO3 in methanol gives ethyl 2-(methoxyimino)-3-oxobutyrate (II),which is brominated with Br2 in CHCl3 yielding ethyl 4-bromo-2-(methoxyimino)-3-oxobutyrate (III).The cyclization of (III) with thiourea (IV) in refluxing ethanol affords ethyl 2-(2-aminothiazol-4-yl)-2-(methoxyimino)acetate (V),which is acylated with chloroacetyl chloride (VI) in DMA to give the corresponding N-chloroacetyl derivative (VII).The hydrolysis of (VII) with KOH in ethanol-water affords 2-(2-chloroacetamidothiazol-4-yl)-2-(methoxyimino)acetic acid (VIII),which is condensed with desacetoxycephalosporanic acid (IX) by means of N-hydroxysuccinimide (NOHS) and dicyclohexylcarbodiimide (DCC) in THF yielding 7beta-[2-(2-chloroacetamidothiazol-4-yl)-2(Z)-(methoxyimino)acetamido]desacetoxycephalosporanic acid (X).The deprotection of (X) with sodium acetate in THF gives the free acid (XI),which is finally esterified with pivaloyloxymethyl bromide (XII) by means of NaHCO3 in ethyl acetate-DMSO.
📌 参考资料/链接：
参考文献标题:Cephalosporin derivatives for oral administration
文献作者:Nakao,H.; Sugawara,S.(Sankyo Co.,Ltd.)
参考来源:DE 3020625
📄 详细内容
合成路线:The methylation of ethyl 2-(hydroxyimino)-3-oxobutyrate (I) with dimethyl sulfate and Na2CO3 in methanol gives ethyl 2-(methoxyimino)-3-oxobutyrate (II),which is brominated with Br2 in CHCl3 yielding ethyl 4-bromo-2-(methoxyimino)-3-oxobutyrate (III).The cyclization of (III) with thiourea (IV) in refluxing ethanol affords ethyl 2-(2-aminothiazol-4-yl)-2-(methoxyimino)acetate (V),which is acylated with chloroacetyl chloride (VI) in DMA to give the corresponding N-chloroacetyl derivative (VII).The hydrolysis of (VII) with KOH in ethanol-water affords 2-(2-chloroacetamidothiazol-4-yl)-2-(methoxyimino)acetic acid (VIII),which is condensed with desacetoxycephalosporanic acid (IX) by means of N-hydroxysuccinimide (NOHS) and dicyclohexylcarbodiimide (DCC) in THF yielding 7beta-[2-(2-chloroacetamidothiazol-4-yl)-2(Z)-(methoxyimino)acetamido]desacetoxycephalosporanic acid (X).The deprotection of (X) with sodium acetate in THF gives the free acid (XI),which is finally esterified with pivaloyloxymethyl bromide (XII) by means of NaHCO3 in ethyl acetate-DMSO.
参考文献标题:Cephalosporin derivatives,process for their preparation and medicines containing them
文献作者:Ochiai,M.; Morimoto,A.; Matsushita,Y.(Takeda Chemical Industries,Ltd.)
参考来源:DE 2715385
合成路线:The methylation of ethyl 2-(hydroxyimino)-3-oxobutyrate (I) with dimethyl sulfate and Na2CO3 in methanol gives ethyl 2-(methoxyimino)-3-oxobutyrate (II),which is brominated with Br2 in CHCl3 yielding ethyl 4-bromo-2-(methoxyimino)-3-oxobutyrate (III).The cyclization of (III) with thiourea (IV) in refluxing ethanol affords ethyl 2-(2-aminothiazol-4-yl)-2-(methoxyimino)acetate (V),which is acylated with chloroacetyl chloride (VI) in DMA to give the corresponding N-chloroacetyl derivative (VII).The hydrolysis of (VII) with KOH in ethanol-water affords 2-(2-chloroacetamidothiazol-4-yl)-2-(methoxyimino)acetic acid (VIII),which is condensed with desacetoxycephalosporanic acid (IX) by means of N-hydroxysuccinimide (NOHS) and dicyclohexylcarbodiimide (DCC) in THF yielding 7beta-[2-(2-chloroacetamidothiazol-4-yl)-2(Z)-(methoxyimino)acetamido]desacetoxycephalosporanic acid (X).The deprotection of (X) with sodium acetate in THF gives the free acid (XI),which is finally esterified with pivaloyloxymethyl bromide (XII) by means of NaHCO3 in ethyl acetate-DMSO.
参考文献标题:CEFETAMET PIVOXIL < Prop INNM >
文献作者:Prous,J.; Castar,J.
参考来源:Drugs Fut 1989,14(5),420
产品链接: CAS No. 65243-33-6››