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【结 构 式】 
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【分子编号】40052 【品名】4-nitrobenzyl (6R,7R)-3-hydroxy-8-oxo-7-[[2-(2-thienyl)acetyl]amino]-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate 【CA登记号】 |
【 分 子 式 】C20H17N3O7S2 【 分 子 量 】475.503 【元素组成】C 50.52% H 3.6% N 8.84% O 23.55% S 13.49% |
合成路线1
该中间体在本合成路线中的序号：(III)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.
| 【1】 Bogan, J.A.; Castaner, J.; Cefaclor. Drugs Fut 1977, 2, 6, 369. |
| 【2】 Chauvette, R.R. (Eli Lilly and Company); Alpha-aminoacyl-3-halo-cephalosporins. DE 2408698; ES 423531; FR 2218877; GB 1461323; JP 49110689; JP 56138190 . |
| 【3】 Chauvette, R.R.; Pennington, P.A.; Chemistry of cephalosporin antibiotics. 30. 3-Methoxy- and 3-halo-3-cephems. J Med Chem 1975, 18, 4, 403-8. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (A) | 15673 | 2-(2-thienyl)acetyl chloride; 2-Thiopheneacetyl chloride | 39098-97-0 | C6H5ClOS | 详情 | 详情 |
| (I) | 40050 | 4-nitrobenzyl (6R,7R)-7-amino-3-methylene-8-oxo-5-thia-1-azabicyclo[4.2.0]octane-2-carboxylate | C15H15N3O5S | 详情 | 详情 | |
| (II) | 40051 | 4-nitrobenzyl (6R,7R)-7-amino-3-hydroxy-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate | C14H13N3O6S | 详情 | 详情 | |
| (III) | 40052 | 4-nitrobenzyl (6R,7R)-3-hydroxy-8-oxo-7-[[2-(2-thienyl)acetyl]amino]-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate | C20H17N3O7S2 | 详情 | 详情 | |
| (IV) | 40053 | 4-nitrobenzyl (6R,7R)-3-chloro-8-oxo-7-[[2-(2-thienyl)acetyl]amino]-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate | C20H16ClN3O6S2 | 详情 | 详情 | |
| (V) | 40054 | 4-nitrobenzyl (6R,7R)-7-amino-3-chloro-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate | C14H12ClN3O5S | 详情 | 详情 | |
| (VI) | 40056 | 4-nitrobenzyl (6R,7R)-7-[[(2R)-2-amino-2-phenylethanoyl]amino]-3-chloro-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate | C22H19ClN4O6S | 详情 | 详情 | |
| (VII) | 40057 | (6R,7R)-7-amino-3-chloro-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid | C7H7ClN2O3S | 详情 | 详情 | |
| (VIII) | 40058 | 4-(chloromethyl)-2,3,5-trimethylphenyl methyl ether; 2-(chloromethyl)-5-methoxy-1,3,4-trimethylbenzene | C11H15ClO | 详情 | 详情 |