【药物名称】Cefaclor, S-6472, Raniclor, Dystaclor MR, Ceclor, L-Kefral
化学结构式(Chemical Structure):
参考文献No.47600
标题:Alpha-aminoacyl-3-halo-cephalosporins
作者:Chauvette, R.R. (Eli Lilly and Company)
来源:DE 2408698; ES 423531; FR 2218877; GB 1461323; JP 49110689; JP 56138190
合成路线图解说明:

The ozonolysis of p-nitrobenzyl ester of 7-amino-3-methylenecephem-4-carboxylic acid (I) in CH2Cl2 gives the p-nitrobenzyl ester of 7-amino-3-hydroxy-3-cephem-4-carboxylic acid (II), which is then condensed with thiophene-2-acetyl chloride (A) in aqueous THF to afford p-nitrobenzyl ester of 7-(thiophene-2-acetamido)-3-hydroxy-3-cephem-4-carboxylic acid (III). The chlorination of (III) with SOCl2, PCl3, POCl3, (COCl)2 or COCl2 in DMF yields p-nitrobenzyl ester of 7-(thiophene-2-acetamido)-3-chloro-3-cephem-4-carboxylic acid (IV), which is then partially hydrolyzed with dry pyridine and PCl5 giving p-nitrobenzyl ester of 7-amino-3-chloro-3-cephem-4-carboxylic acid (V). This compound can be acylated easily to p-nitrobenzyl ester of 7-(D-alpha-phenylglycylamido)-3-chloro-3-cephem-4-carboxylic acid (VI), which is finally hydrogenolyzed with Zn and conc. HCl. An alternative way starting also from (V) is its hydrogenolysis with H2 over Pd/C in THF-MeOH giving the 7-amino-3-chloro-3-cephem-4-carboxylic acid (VII), which is then acylated as usual.

参考文献No.76176
标题:Chemistry of cephalosporin antibiotics. 30. 3-Methoxy- and 3-halo-3-cephems
作者:Chauvette, R.R.; Pennington, P.A.
来源:J Med Chem 1975,18(4),403-8
合成路线图解说明:

The ozonolysis of p-nitrobenzyl ester of 7-amino-3-methylenecephem-4-carboxylic acid (I) in CH2Cl2 gives the p-nitrobenzyl ester of 7-amino-3-hydroxy-3-cephem-4-carboxylic acid (II), which is then condensed with thiophene-2-acetyl chloride (A) in aqueous THF to afford p-nitrobenzyl ester of 7-(thiophene-2-acetamido)-3-hydroxy-3-cephem-4-carboxylic acid (III). The chlorination of (III) with SOCl2, PCl3, POCl3, (COCl)2 or COCl2 in DMF yields p-nitrobenzyl ester of 7-(thiophene-2-acetamido)-3-chloro-3-cephem-4-carboxylic acid (IV), which is then partially hydrolyzed with dry pyridine and PCl5 giving p-nitrobenzyl ester of 7-amino-3-chloro-3-cephem-4-carboxylic acid (V). This compound can be acylated easily to p-nitrobenzyl ester of 7-(D-alpha-phenylglycylamido)-3-chloro-3-cephem-4-carboxylic acid (VI), which is finally hydrogenolyzed with Zn and conc. HCl. An alternative way starting also from (V) is its hydrogenolysis with H2 over Pd/C in THF-MeOH giving the 7-amino-3-chloro-3-cephem-4-carboxylic acid (VII), which is then acylated as usual.

参考文献No.800623
标题:Cefaclor
作者:Bogan, J.A.; Casta馿r, J.
来源:Drugs Fut 1977,2(6),369
合成路线图解说明:

The ozonolysis of p-nitrobenzyl ester of 7-amino-3-methylenecephem-4-carboxylic acid (I) in CH2Cl2 gives the p-nitrobenzyl ester of 7-amino-3-hydroxy-3-cephem-4-carboxylic acid (II), which is then condensed with thiophene-2-acetyl chloride (A) in aqueous THF to afford p-nitrobenzyl ester of 7-(thiophene-2-acetamido)-3-hydroxy-3-cephem-4-carboxylic acid (III). The chlorination of (III) with SOCl2, PCl3, POCl3, (COCl)2 or COCl2 in DMF yields p-nitrobenzyl ester of 7-(thiophene-2-acetamido)-3-chloro-3-cephem-4-carboxylic acid (IV), which is then partially hydrolyzed with dry pyridine and PCl5 giving p-nitrobenzyl ester of 7-amino-3-chloro-3-cephem-4-carboxylic acid (V). This compound can be acylated easily to p-nitrobenzyl ester of 7-(D-alpha-phenylglycylamido)-3-chloro-3-cephem-4-carboxylic acid (VI), which is finally hydrogenolyzed with Zn and conc. HCl. An alternative way starting also from (V) is its hydrogenolysis with H2 over Pd/C in THF-MeOH giving the 7-amino-3-chloro-3-cephem-4-carboxylic acid (VII), which is then acylated as usual.

Drug Information Express,Drug R&D,Chemical Database,Patent Search.
Copyright © 2006-2024 Drug Future. All rights reserved.Contact Us