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【结 构 式】 
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【分子编号】38203 【品名】2-[2-[(tert-butoxycarbonyl)amino]-5-chloro-1,3-thiazol-4-yl]-2-[(trityloxy)imino]acetic acid 【CA登记号】 |
【 分 子 式 】C29H26ClN3O5S 【 分 子 量 】564.06136 【元素组成】C 61.75% H 4.65% Cl 6.29% N 7.45% O 14.18% S 5.68% |
合成路线1
该中间体在本合成路线中的序号：(VII)Bicyclic enol compound (I) was phosphorylated by means of diphenyl phosphorochloridate and diisopropylethylamine, and the resulting enol phosphate was displaced with thioacetic acid yielding thioacetate ester (II). Cleavage of the phenylacetamido group of (II) to afford amine (III) was then effected by treatment with PCl5 and pyridine, followed by quenching with isobutyl alcohol. On the other side, thiazole (IV) was chlorinated with N-chlorosuccinimide to provide the 5-chlorothiazole (V). Protection of the amino group of (V) with di-tert-butyl dicarbonate, followed by ester hydrolysis gave (VI). The oximino group of (VI) was then protected as the O-trityl derivative (VII) by treatment with triphenylmethyl chloride. Coupling of carboxylic acid (VII) with amine (III) employing POCl3 and pyridine provided amide (VIII). Optionally, hydrolysis of the thioacetate ester using morpholine and pyridine, followed by S-alkylation with chloroiodomethane furnished the chloromethylsulfanyl derivative (IX).
| 【1】 Oh, S.H.; Lee, C.-S.; Ryu, E.-J.; Paek, K.-S.; Kim, M.Y.; Youn, H.; Synthesis and antibacterial activities of novel C(3)-aminopyrimidinyl substituted cephalosporins including against respiratory tract pathogens. Bioorg Med Chem Lett 2000, 10, 18, 2123. |
| 【2】 Paek, K.S.; Ryu, E.J.; Oh, S.H.; Lee, C.S.; Lee, S.H.; Kim, M.Y.; Synthesis and antibacterial activities of LB10827, a new oral cephalosporin antibiotic. 39th Intersci Conf Antimicrob Agents Chemother (Sept 26 1999, San Francisco) 1999, Abst F397. |
| 【3】 Kim, M.Y.; Oh, S.H.; Kim, Y.Z.; Moon, K.Y.; Lee, C.S.; Ryu, E.J.; Paek, K.S.; Lee, S.H. (LG Chem Ltd.); Novel cephalosporin cpds., processes for preparation thereof and antimicrobial compsns. containing the same. WO 9958535 . |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (I) | 38210 | benzhydryl 3-hydroxy-8-oxo-7-[(2-phenylacetyl)amino]-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate | C28H24N2O5S | 详情 | 详情 | |
| (II) | 38199 | benzhydryl 3-(acetylsulfanyl)-8-oxo-7-[(2-phenylacetyl)amino]-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate | C30H26N2O5S2 | 详情 | 详情 | |
| (III) | 38200 | benzhydryl 3-(acetylsulfanyl)-7-amino-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate | C22H20N2O4S2 | 详情 | 详情 | |
| (IV) | 15889 | Ethyl 2-(2-aminothiazol-4-yl)-2-hydroxyiminoacetate;(Z)-ethyl 2-(2-aminothiazol-4-yl)-2-(hydroxyimino)acetate； ethyl 2-(2-amino-1,3-thiazol-4-yl)-2-(hydroxyimino)acetate | 60845-81-0 | C7H9N3O3S | 详情 | 详情 |
| (V) | 38201 | ethyl 2-(2-amino-5-chloro-1,3-thiazol-4-yl)-2-(hydroxyimino)acetate | C7H8ClN3O3S | 详情 | 详情 | |
| (VI) | 38202 | 2-[2-[(tert-butoxycarbonyl)amino]-5-chloro-1,3-thiazol-4-yl]-2-(hydroxyimino)acetic acid | C10H12ClN3O5S | 详情 | 详情 | |
| (VII) | 38203 | 2-[2-[(tert-butoxycarbonyl)amino]-5-chloro-1,3-thiazol-4-yl]-2-[(trityloxy)imino]acetic acid | C29H26ClN3O5S | 详情 | 详情 | |
| (VIII) | 38204 | benzhydryl 3-(acetylsulfanyl)-7-([2-[2-[(tert-butoxycarbonyl)amino]-5-chloro-1,3-thiazol-4-yl]-2-[(trityloxy)imino]acetyl]amino)-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate | C51H44ClN5O8S3 | 详情 | 详情 | |
| (IX) | 38205 | benzhydryl 7-([2-[2-[(tert-butoxycarbonyl)amino]-5-chloro-1,3-thiazol-4-yl]-2-[(trityloxy)imino]acetyl]amino)-3-[(chloromethyl)sulfanyl]-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate | C50H43Cl2N5O7S3 | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(II)Coupling of the amino cephem derivative (I) with oximino acid (II) by means of POCl3/pyridine produces amide (III). Subsequent condensation of (III) with bis(dimethylamino)t-butoxymethane affords enamine (IV), which is further hydrolyzed to aldehyde (V) under acidic conditions. Treatment of aldehyde (V) with trifluoromethanesulfonic anhydride and pyridine produces the vinyl triflate (VI)
| 【1】 Lee, C.; Kim, G.; Jang, Y.; Koo, K.; Cho, Y.; Youn, H.; Synthesis and antibacterial activities of LB11058, a novel anti-MRSA cephalosporin antibiotic. 42nd Intersci Conf Antimicrob Agents Chemother (Sept 27 2002, San Diego) 2002, Abst F-329. |
| 【2】 Lee, S.-H.; Lee, C.-S.; Ryu, E.-J.; Jang, Y.-J.; Kim, G.-T.; Cho, Y.-r.; Joo, H.-Y.; Shin, J.-E.; Koo, K.-D. (LG Chem Ltd.); Novel cephalosporin cpds. and process for preparing the same. WO 0372582 . |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (I) | 61475 | benzhydryl (6R,7R)-7-amino-3-methyl-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate | C21H20N2O3S | 详情 | 详情 | |
| (II) | 38203 | 2-[2-[(tert-butoxycarbonyl)amino]-5-chloro-1,3-thiazol-4-yl]-2-[(trityloxy)imino]acetic acid | C29H26ClN3O5S | 详情 | 详情 | |
| (III) | 61476 | benzhydryl (6R,7R)-7-({2-{2-[(tert-butoxycarbonyl)amino]-5-chloro-1,3-thiazol-4-yl}-2-[(trityloxy)imino]acetyl}amino)-3-methyl-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate | C50H44ClN5O7S2 | 详情 | 详情 | |
| (IV) | 61477 | benzhydryl (6R,7R)-7-({2-{2-[(tert-butoxycarbonyl)amino]-5-chloro-1,3-thiazol-4-yl}-2-[(trityloxy)imino]acetyl}amino)-3-[(E)-2-(dimethylamino)ethenyl]-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate | C53H49ClN6O7S2 | 详情 | 详情 | |
| (V) | 61478 | benzhydryl (6R,7R)-7-({2-{2-[(tert-butoxycarbonyl)amino]-5-chloro-1,3-thiazol-4-yl}-2-[(trityloxy)imino]acetyl}amino)-8-oxo-3-(3-oxopropyl)-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate | C52H46ClN5O8S2 | 详情 | 详情 | |
| (VI) | 61479 | benzhydryl (6R,7R)-7-({2-{2-[(tert-butoxycarbonyl)amino]-5-chloro-1,3-thiazol-4-yl}-2-[(trityloxy)imino]acetyl}amino)-8-oxo-3-((E)-2-{[(trifluoromethyl)sulfonyl]oxy}ethenyl)-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate | C52H43ClF3N5O10S3 | 详情 | 详情 |