超声波探伤探头:头孢噻肟钠 [CAS:64485-93-4]合成路线图解??有机化学网

药物详细合成路线

Chemical Name： (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 Generic Name： 头孢噻肟钠;Cefotaxime sodium Other Names： Cefotaxime sodium;HR-756;Claforan CAS： 64485-93-4 Related CAS： 63527-52-6 (free base) Formula： C₁₆H₁₆N₅NaO₇S₂ Mole Weight： 477.45302 structure： Company： Aventis Pharma (Originator), Abbott (Licensee) Usage： Antibacterial Drugs, ANTIINFECTIVE THERAPY, Cephalosporins Route 1 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. Intermediates: Serial No. methyl (1S,3aS,4S,5S,7aS)-4-(cyanomethyl)-7a-methyl-5-[(1R,3R,6R)-3-methyl-2-oxo-7-oxabicyclo[4.1.0]hept-3-yl]octahydro-1H-indene-1-carboxylate (A) methyl (1S,3aS,4S,5S,7aS)-4-(cyanomethyl)-7a-methyl-5-[(1R)-1-methyl-2,4-dioxocyclohexyl]octahydro-1H-indene-1-carboxylate (X) methyl (1S,3aS,4S,5S,7aS)-4-(2-amino-2-oxoethyl)-5-[(1R)-2-methoxy-1-methyl-4-oxo-2-cyclohexen-1-yl]-7a-methyloctahydro-1H-indene-1-carboxylate (I) [2-[2-(chloromethyl)-1H-imidazol-1-yl]-5-nitrophenyl](2-chlorophenyl)methanone (VIII) (7S,11S,12S,13S,14R,15R,16R,17S,18S)-26-formyl-2,15,17,27,29-pentahydroxy-11-methoxy-3,7,12,14,16,18,22-heptamethyl-6,23-dioxo-8,30-dioxa-24-azatetracyclo[23.3.1.1(4,7).0(5,28)]triaconta-1(28),1(29),2,4,9,19,21,25,27-nonaen-13-yl acetate; 3-Formyirifamycin SV (IX) tert-butyl (1R)-1-[(1S)-2-[(2S)-2-([[(1S)-2-amino-1-methyl-2-oxoethyl]amino]carbonyl)pyrrolidinyl]-1-hydroxy-2-oxoethyl]-3-methylbutylcarbamate (IV) (2R,3S)-3-([[methyl(dimethylene)-lambda(6)-sulfanyl]oxy]methyl)-2-phenyl-2,3-dihydro-1,5-benzothiazepin-4(5H)-one (III) (3S)-3-(3-methylphenyl)-2,3-dihydro-1H-1,2-benzisothiazole-1,1-dione (B) 4-ethyl-3,14-dioxo-3,4,12,14-tetrahydro-1H-pyrano[3,4:6,7]indolizino[1,2-b]quinolin-4-yl 2-{[2-amino-3-(1H-imidazol-5-yl)propanoyl]amino}-3-methylbutanoate (VI) 2-methyl-6-[(4-nitrophenyl)oxy]tetrahydro-2H-pyran-3,4,5-triol (VII) 2-methyl-4-(methyloxy)-6-[(4-nitrophenyl)oxy]tetrahydro-2H-pyran-3,5-diol (II) 2-[(4-aminophenyl)oxy]-6-methyl-4-(methyloxy)tetrahydro-2H-pyran-3,5-diol (V) Reference 1:     Neuman, M.; Castaner, J.; HR-756. Drugs Fut 1978, 3, 10, 749. Reference 2:     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 52102293; JP 5247013 .