药物详细合成路线

Name	Cefotaxime sodium;HR-756;Claforan
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
CAS	64485-93-4
Related CAS	63527-52-6 (free base)
Formula	C16H16N5NaO7S2
Structure
Formula Weight	477.45302
Stage	上市-1980
Company	Aventis Pharma (Originator), Abbott (Licensee)
Activity/Mechanism	Antibacterial Drugs, ANTIINFECTIVE THERAPY, Cephalosporins
Syn. Route	1

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. List of intermediates 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 .

来源:药化网

作者:药化小编

摘要:本文合成路线介绍的是药物中文名头孢噻肟钠；英文名Cefotaxime sodium;HR-756;Claforan；CAS[64485-93-4]

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