Cefonicid sodium, SK&F-D-75073-Z2, Monocid

头孢尼西钠 头孢尼西 Chemical Name: [6R-[6alpha,7beta(R*)]]-7-[(Hydroxyphenylacetyl)amino]-8-oxo-3-[[[1-(sulfomethyl)-1H-tetrazol-5-yl]thio]methyl]-5-thia]-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid disodium salt; (6R,7R)-[(R)-Mandelamido]-8-oxo-3-[[[(1-sulfomethyl)-1H-tetrazol-5-yl]thio]methyl]-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid disodium salt
CAS No. 61270-78-8, 61270-58-4 (free acid)
项目整合开发状态: Launched-1984
项目研究机构: GlaxoSmithKline (Originator)
合成路线:The reaction of aminomethansulfonic acid (I) with phthalic anhydride (II) by means of potassium acetate in refluxing acetic acid gives phthalimidomethansulfonic acid (III),which by reaction with PCl5 in refluxing benzene is converted into its acyl chloride (IV).The condensation of (IV) with tert-butylamine (A) in CHCl3 affords N-tert-butylphthalimidomethansulfonamide (V),which by reaction with hydrazine hydrate in refluxing ethanol yields 2-aminomethan-N-tert-butylsulfonamide (VI).The reaction of (VI) with CS2 and MeI by means of triethylamine in ethanol gives N-tert-butylsulfamoylmethyldithiocarbamic acid methyl ester (VII),which is cyclized with NaN3 in hot water to afford 1-(N-tert-butylsulfamoylmethyl)tetrazol-5-thiol (VIII).The hydrolysis of (VIII) with trifluoroacetic acid yields compound 1-sulfamoylmethyltetrazol-5-thiol (IX).

合成路线:Compound 1-sulfamoylmethyltetrazol-5-thiol (IX) can also be obtained by reaction of (I) with CS2 and MeI by means of KOH in refluxing ethanol to give sulfomethyldithiocarbamic acid methyl ester (XIII),which is then cyclized with NaN3 in hot water.

合成路线:a) By reaction of 1-sulfamoylmethyltetrazol-5-thiol (IX) with 7-mandelamidocephalosporanic acid (XII) by means of NaHCO3.b) ByCondensation of 1-sulfamoylmethyltetrazol-5-thiol (IX) with 7-aminocephalosporanic acid (X) by means of NaHCO3 in acetone - water to give 7-amino-3-(1-sulfamoyl-methyltetrazol-5-ylthio-methyl)-3-cephem-4-carboxylic acid (XI).Finally,this compound is acylated with D-O-dichloroacetylmandeloyl chloride (A) by means of NaHCO3 in acetone-water to afford the target compound.b) ByCondensation of 1-sulfamoylmethyltetrazol-5-thiol (IX) with 7-aminocephalosporanic acid (X) by means of NaHCO3 in acetone - water to give 7-amino-3-(1-sulfamoyl-methyltetrazol-5-ylthio-methyl)-3-cephem-4-carboxylic acid (XI).Finally,this compound is acylated with D-O-dichloroacetylmandeloyl chloride (A) by means of NaHCO3 in acetone-water to afford the target compound.