合成路线:A new process for the preparation of cefpodoxime,which can be converted into cefpodoxime proxetil by known methods,has been described:The condensation of 2-(2-aminothiazol-4-yl)-2(Z)-(methoxyimino)acetic acid 2-benzothiazolyl ester (I) with (6R,7R)-7-amino-3-(methoxymethyl)-3-cephem-4-carboxylic acid (II) by means of an organic base such as Et3N,pyridine,N-methylpiperidine,DBU or DMAP in either THF/water,acetone/water,DMF/water,dimethylacetamide or dichloromethane directly gives cefpodoxime (III).
参考文献标题:Process for the preparation of cefpodoxime acid
文献作者:Nizar,H.; Singh,K.; Khanna,J.M.; Kumar,Y.; De,S.; Arora,R.K.(Ranbaxy Laboratories Ltd.)
参考来源:WO 0068234
合成路线:The condensation of 7-amino-3-(methoxymethyl)-3-cephem-4-carboxylic acid (I) with 4-bromo-2-(methoxyimino)-3-oxobutyric acid (II) by means of PCl5 and HMDS in dichloromethane gives the butyramide (III),which is cyclized with thiourea (IV) by means of Na-OAc in water to yield the thiazol derivative (IV).Finally,the carboxy group of (IV) is esterified with 1-iodoethyl isopropyl carbonate (VI) by means of DBU in DMA to afford the target cefpodoxime proxetil.
参考文献标题:Process for the preparation of cefpodoxime acid
文献作者:Kumar,Y.; Nizar,H.; Tewari,N.; Rai,B.P.; Aryan,R.C.(Ranbaxy Laboratories Ltd.)
参考来源:WO 0283634
合成路线:1) The methanolysis of 3-(acetoxymethyl)-7-[4-chloro-3-oxo-2(Z)-(methoxyimino)butyrylamidol-3-cephem-4-carboxylic acid (I) with methanol and NaHCO3 gives the corresponding 3-(methoxymethyl) derivative (II),which is esterified with 1-iodoethylisopropyl carbonate (III) by means of dicyclohexylamine or tetramethylguanidine or DIEA (diisopropylethylamine) in DMA to afford the corresponding ester (IV).Finally,this compound is cyclized with thiourea (V) and methyl iodide in a phosphate buffer.
合成路线:2) The free acid (II) can be cyclized with thiourea in a similar way as before to give 7-[2 (2-amino-thiazol-4-yl)-2-(Z)-(methoxyimino)acetamido]-3-(methoxymethyl)-3-cephem 4-carboxylic acid (VI),which is finally esterified with the iodoester (III) as before.
合成路线:3) The iodoester (III) is obtained as follows: The chlorination of ethyl chloroformate (VII) with SO2Cl2 and benzoyl peroxide gives 1-chloroethyl-chloroformate (VIII),which is esterified with o-propanol in pyridine to afford 1-chloroethyl isopropyl carbonate (IX).Finally,this compound is iodinated with NaI and 18-crown-6 in refluxing benzene.
参考文献标题:Cefpodoxime Proxetil
文献作者:Castar,J.; Serradell,M.N.
参考来源:Drugs Fut 1988,13(1),16
合成路线:1) The methanolysis of 3-(acetoxymethyl)-7-[4-chloro-3-oxo-2(Z)-(methoxyimino)butyrylamidol-3-cephem-4-carboxylic acid (I) with methanol and NaHCO3 gives the corresponding 3-(methoxymethyl) derivative (II),which is esterified with 1-iodoethylisopropyl carbonate (III) by means of dicyclohexylamine or tetramethylguanidine or DIEA (diisopropylethylamine) in DMA to afford the corresponding ester (IV).Finally,this compound is cyclized with thiourea (V) and methyl iodide in a phosphate buffer.
参考文献标题:An improved process for the preparation of cefpodoxime proxetil
文献作者:Subramanian,S.; Deshpande,P.B.; Deshpande,P.N.; Luthra,P.K.; Das,G.K.; Kamma,R.(Orchid Chemicals & Pharmaceuticals Ltd.)
参考来源:WO 0448387
合成路线:The condensation of 7-amino-3-(methoxymethyl)-3-cephem-4-carboxylic acid (I) with 4-bromo-2-(methoxyimino)-3-oxobutyric acid (II) by means of PCl5 and HMDS in dichloromethane gives the butyramide (III),which is cyclized with thiourea (IV) by means of Na-OAc in water to yield the thiazol derivative (IV).Finally,the carboxy group of (IV) is esterified with 1-iodoethyl isopropyl carbonate (VI) by means of DBU in DMA to afford the target cefpodoxime proxetil.
参考文献标题:A process for the manufacture of cefpodoxime proxetil
文献作者:Gharpure,M.M.; Deshmukh,S.S.; Mahale,R.D.(Lupin Ltd.)
参考来源:WO 0460896
合成路线:1) The methanolysis of 3-(acetoxymethyl)-7-[4-chloro-3-oxo-2(Z)-(methoxyimino)butyrylamidol-3-cephem-4-carboxylic acid (I) with methanol and NaHCO3 gives the corresponding 3-(methoxymethyl) derivative (II),which is esterified with 1-iodoethylisopropyl carbonate (III) by means of dicyclohexylamine or tetramethylguanidine or DIEA (diisopropylethylamine) in DMA to afford the corresponding ester (IV).Finally,this compound is cyclized with thiourea (V) and methyl iodide in a phosphate buffer.
合成路线:2) The free acid (II) can be cyclized with thiourea in a similar way as before to give 7-[2 (2-amino-thiazol-4-yl)-2-(Z)-(methoxyimino)acetamido]-3-(methoxymethyl)-3-cephem 4-carboxylic acid (VI),which is finally esterified with the iodoester (III) as before.
合成路线:3) The iodoester (III) is obtained as follows: The chlorination of ethyl chloroformate (VII) with SO2Cl2 and benzoyl peroxide gives 1-chloroethyl-chloroformate (VIII),which is esterified with o-propanol in pyridine to afford 1-chloroethyl isopropyl carbonate (IX).Finally,this compound is iodinated with NaI and 18-crown-6 in refluxing benzene.
参考文献标题:Studies on orally active cephalosporin esters
文献作者:Fujimoto,K.; Ishihara,S.; Yanagisawa,H.; Ide,J.; Nakayama,E.; Nakao,H.; Sugawara,S.; Iwata,M.
参考来源:J Antibiot 1987,40(3),370
产品链接: CAS No. 87239-81-4››