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Name Cefmenoxime hydrochloride;SCE-1365(free acid);Bestron;Cemix;Tacef;Bestcall
Chemical Name 7beta-[2-(2-Aminothiazol-4-yl)-(Z)-2-(methoxyiminoacetamido)]-3-[(1-methyl-1H-tetrazol-5-yl)thiomethyl]ceph-3-em-4-carboxylic acid hemihydrochloride;7-[[(2-Amino-4-thiazolyl)(methoxyimino)acetyl]amino]-3-[[(1-methyl-1H-tetrazol-5-yl)thio]methyl]-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid hemihydrochloride
CAS 75738-58-8
Related CAS
Formula C16H18ClN9O5S3
Structure
Formula Weight 548.02416
Stage 上市-1983
Company Senju (Originator), Takeda (Originator), Grelan (Marketer), Kyorin (Comarketer)
Activity/Mechanism Antibiotics, ANTIINFECTIVE THERAPY, Cephalosporins
Syn. Route 2
Route 1
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.
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 (iii)
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 (iv)
[2-[2-(chloromethyl)-1h-imidazol-1-yl]-5-nitrophenyl](2-chlorophenyl)methanone (i)
(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 (ii)
2-bromo-4-(2-chlorophenyl)-9-methyl-4h,6h-thieno[2,3-e][1,2,4]triazolo[3,4-c][1,4]oxazepine (v)
4-[5-bromo-3-[bromo(2-chlorophenyl)methyl]-2-thienyl]-3-(chloromethyl)-5-methyl-4h-1,2,4-triazole (vi)
tert-butyl (1s)-2-[[(1s)-2-amino-1-benzyl-2-oxoethyl]amino]-1-benzyl-2-oxoethylcarbamate (xii)
methyl (2s,3r,4s,5r,6r)-3,4,5-tris(acetoxy)-6-hydroxytetrahydro-2h-pyran-2-carboxylate (xi)
(vii)
(viii)
(ix)
(x)
Reference 1:
    ochiai, m.; et al.; new cephalosporin derivatives with high antibacterial activities. chem pharm bull 1977, 25, 11, 3115-17.
Reference 2:
    ochiai, m.; et al.; cephalosporin derivatives and their preparation. be 0853545; jp 52125188; za 7702030 .
Reference 3:
    ochiai, m.; et al. (takeda chemical industries, ltd.); thiazolylacetamido cephasloporin type compounds. de 2556736; es 464772; fr 2294690; gb 1536283; nl 7514811; us 4098888 .
Reference 4:
    serradell, m.n.; castaner, j.; blancafort, p.; sce-1365. drugs fut 1980, 5, 3, 146.

Route 2
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.
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)
4-[5-bromo-3-[bromo(2-chlorophenyl)methyl]-2-thienyl]-3-(chloromethyl)-5-methyl-4h-1,2,4-triazole (vi)
(vii)
(xiii)
(xiv)
Reference 1:
    ochiai, m.; et al.; new cephalosporin derivatives with high antibacterial activities. chem pharm bull 1977, 25, 11, 3115-17.
Reference 2:
    ochiai, m.; et al.; cephalosporin derivatives and their preparation. be 0853545; jp 52125188; za 7702030 .
Reference 3:
    serradell, m.n.; castaner, j.; blancafort, p.; sce-1365. drugs fut 1980, 5, 3, 146.

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盐酸头孢甲肟;英文名Cefmenoxime hydrochloride;SCE-1365(free acid);Bestron;Cemix;Tacef;Bestcall;CAS[75738-58-8]

 
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