Ceftazidime, LY-139381, GR-20263, Fortam, Glazidim, Fortum, Modacin, Tazidime, Tazicef, Pentacef, Fortaz, Ceptaz

头孢他啶Chemical Name: (6R,7R)-7-[2-(2-amino-1,3-thiazol-4-yl)-2(Z)-(1-carboxy-1-methylethyloxyimino)acetamido]-8-oxo-3-(1-pyridiniumylmethyl)-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate pentahydrate
CAS No. 78439-06-2
项目整合开发状态: Launched-1984
项目研究机构: GlaxoSmithKline (Originator), Tanabe Seiyaku (Licensee)
合成路线:The reaction of ethyl acetoacetate (I) with NaNO2 in acetic acid-water gives ethyl 2-(hydroxyimino)-3-oxobutyrate (II),which is cyclized with thiourea (III) by means of SO2Cl2 in methylene chloride yielding ethyl 2-(2-aminothiazol-4-yl)-2-(hydroxyimino)acetate (IV).The treatment of (IV) with trityl chloride (V) and triethylamine in DMF affords ethyl 2-(hydroxyimino)-2-(2-tritylaminothiazol-4-yl)acetate (VI),which by condensation with tert-butyl 2-bromo-2-methylpropionate (VII) by means of K2CO3 in DMSO is converted into ethyl 2-(2-tert-butoxycarbonyl-2-propyloxymino)-2-(2-tritylaminothiazol-4-yl)acetate (VIII).The hydrolysis of (VIII) with NaOH in refluxing methanol gives 2-(2-tert-butoxycarbonyl-2-propyloxyimino)-2-(2-tritylaminothiazol-4-yl)acetic acid (IX),which by condensation with tert-butyl 7-aminocephalosporanate (X) by means of 1-hydroxybenzotriazole and dicyclohexylcarbodiimide in DMF yields tert-butyl 7-[2-(2-tert-butoxycarbonyl-2-propyloxyimino)-2-(2-tritylaminothiazol-4-yl)acetamido]cephalosporanate (XI).The hydrolysis of (XI) with trifluoroacetic acid in anisole affords 7-[2-(2-aminothiazol-4-yl)-2-(2-carboxy-2-propyloxyimino)acetamido]cephalosporanic acid (XII),which is finally treated with pyridine (A) and NaI.