合成路线:The methylation of ethyl 3-oxo-2-hydroxyiminobutyrate (I) with dimethyl sulfate and Na2CO3 in methanol gives ethyl 3-oxo-2-methoxyiminobutyrate (II),which is brominated with Br2 in CHCl3 to afford ethyl 4-bromo-3-oxo-2-methoxyiminobutyrate (III).The cyclization of (III) with thiourea (A) in refluxing ethanol affords ethyl 2-(2-aminothiazol-4-yl)-2-methoxyiminoacetate (IV),which is acylated with chloroacetyl chloride in dimethylacetamide to yield ethyl 2-(2-chloroacetamidothiazol-4-yl)-2-methoxyiminoacetate (V).The hydrolysis of (V) with KOH in ethanol-water gives the corresponding free acid (VI),which is treated with PCl5 in methylene chloride to obtain the acyl chloride (VII).The condensation of tert-butyl 7-aminocephalosporanate (VIII) with (VII) by means of pyridine in methylene chloride gives tert-butyl 7-[alpha-methoxyimino-(2-chloroacetamidothiazol-4-yl)acetamido]cephalosporanate (IX),which is desacylated with thiourea and triethylbenzylammonium bromide in THF-ethanol yielding tert-butyl 7-[alpha-methoxyimino-alpha-(2-aminothiazol-4-yl)acetamido]cephalosporanate (X),which is hydrolyzed with trifluoroacetic acid to afford the free cephalosporanic acid (Xl).Finally,this compound is condensed with 1-methyl-5-mercaptotetrazol (XII) by means of NaHCO3 and triethylbenzylammoniurn bromide in water.
合成路线:The condensation of (VII) or the free acid (VI) by means of pyridine or isobutyl chloroformate,respectively,with 7-amino-3-(1-methyl-1H-tetrazol-5-ylthiomethyl)-3-cephem-4-carboxylic acid (XIII) gives 7-[alpha-(2-chloroacetylamidothiazol-4-yl)-alpha-methoxyiminoacetamido]-3-(1-methyl-1H-tetrazol-5-ylthiomethyl)-3-cephem-4-carboxylic acid (XIV),which is finally desacylated with thiourea (A) and benzyltriethylammonium bromide as before.
参考文献标题:SCE-1365
文献作者:Serradell,M.N.; Castar,J.; Blancafort,P.
参考来源:Drugs Fut 1980,5(3),146
合成路线:The methylation of ethyl 3-oxo-2-hydroxyiminobutyrate (I) with dimethyl sulfate and Na2CO3 in methanol gives ethyl 3-oxo-2-methoxyiminobutyrate (II),which is brominated with Br2 in CHCl3 to afford ethyl 4-bromo-3-oxo-2-methoxyiminobutyrate (III).The cyclization of (III) with thiourea (A) in refluxing ethanol affords ethyl 2-(2-aminothiazol-4-yl)-2-methoxyiminoacetate (IV),which is acylated with chloroacetyl chloride in dimethylacetamide to yield ethyl 2-(2-chloroacetamidothiazol-4-yl)-2-methoxyiminoacetate (V).The hydrolysis of (V) with KOH in ethanol-water gives the corresponding free acid (VI),which is treated with PCl5 in methylene chloride to obtain the acyl chloride (VII).The condensation of tert-butyl 7-aminocephalosporanate (VIII) with (VII) by means of pyridine in methylene chloride gives tert-butyl 7-[alpha-methoxyimino-(2-chloroacetamidothiazol-4-yl)acetamido]cephalosporanate (IX),which is desacylated with thiourea and triethylbenzylammonium bromide in THF-ethanol yielding tert-butyl 7-[alpha-methoxyimino-alpha-(2-aminothiazol-4-yl)acetamido]cephalosporanate (X),which is hydrolyzed with trifluoroacetic acid to afford the free cephalosporanic acid (Xl).Finally,this compound is condensed with 1-methyl-5-mercaptotetrazol (XII) by means of NaHCO3 and triethylbenzylammoniurn bromide in water.
合成路线:The condensation of (VII) or the free acid (VI) by means of pyridine or isobutyl chloroformate,respectively,with 7-amino-3-(1-methyl-1H-tetrazol-5-ylthiomethyl)-3-cephem-4-carboxylic acid (XIII) gives 7-[alpha-(2-chloroacetylamidothiazol-4-yl)-alpha-methoxyiminoacetamido]-3-(1-methyl-1H-tetrazol-5-ylthiomethyl)-3-cephem-4-carboxylic acid (XIV),which is finally desacylated with thiourea (A) and benzyltriethylammonium bromide as before.
参考文献标题:Cephalosporin derivatives and their preparation
文献作者:Ochiai,M.; et al.
参考来源:BE 0853545; JP 52125188; ZA 7702030
合成路线:The methylation of ethyl 3-oxo-2-hydroxyiminobutyrate (I) with dimethyl sulfate and Na2CO3 in methanol gives ethyl 3-oxo-2-methoxyiminobutyrate (II),which is brominated with Br2 in CHCl3 to afford ethyl 4-bromo-3-oxo-2-methoxyiminobutyrate (III).The cyclization of (III) with thiourea (A) in refluxing ethanol affords ethyl 2-(2-aminothiazol-4-yl)-2-methoxyiminoacetate (IV),which is acylated with chloroacetyl chloride in dimethylacetamide to yield ethyl 2-(2-chloroacetamidothiazol-4-yl)-2-methoxyiminoacetate (V).The hydrolysis of (V) with KOH in ethanol-water gives the corresponding free acid (VI),which is treated with PCl5 in methylene chloride to obtain the acyl chloride (VII).The condensation of tert-butyl 7-aminocephalosporanate (VIII) with (VII) by means of pyridine in methylene chloride gives tert-butyl 7-[alpha-methoxyimino-(2-chloroacetamidothiazol-4-yl)acetamido]cephalosporanate (IX),which is desacylated with thiourea and triethylbenzylammonium bromide in THF-ethanol yielding tert-butyl 7-[alpha-methoxyimino-alpha-(2-aminothiazol-4-yl)acetamido]cephalosporanate (X),which is hydrolyzed with trifluoroacetic acid to afford the free cephalosporanic acid (Xl).Finally,this compound is condensed with 1-methyl-5-mercaptotetrazol (XII) by means of NaHCO3 and triethylbenzylammoniurn bromide in water.
合成路线:The condensation of (VII) or the free acid (VI) by means of pyridine or isobutyl chloroformate,respectively,with 7-amino-3-(1-methyl-1H-tetrazol-5-ylthiomethyl)-3-cephem-4-carboxylic acid (XIII) gives 7-[alpha-(2-chloroacetylamidothiazol-4-yl)-alpha-methoxyiminoacetamido]-3-(1-methyl-1H-tetrazol-5-ylthiomethyl)-3-cephem-4-carboxylic acid (XIV),which is finally desacylated with thiourea (A) and benzyltriethylammonium bromide as before.
参考文献标题:New cephalosporin derivatives with high antibacterial activities
文献作者:Ochiai,M.; et al.
参考来源:Chem Pharm Bull 1977,25(11),3115-17
产品链接: CAS No. 75738-58-8››