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【结 构 式】 
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【分子编号】15890 【品名】2-[2-[(tert-butoxycarbonyl)amino]-1,3-thiazol-4-yl]-2-(hydroxyimino)acetic acid 【CA登记号】 |
【 分 子 式 】C10H13N3O5S 【 分 子 量 】287.29644 【元素组成】C 41.81% H 4.56% N 14.63% O 27.84% S 11.16% |
合成路线1
该中间体在本合成路线中的序号：(II)1) The protection of the amino group of 2-(2-aminothiazol-4-yl)-2(Z)-(hydroxyimino)acetic acid ethyl ester (I) with di-tert-butyl dicarbonate, dimethylaminopyridine and NaOH gives 2-[2-(tert-butoxycarbonylamino)thiazol-4-yl]-2(Z)-(hydroxyimino)acetic acid (II), which is then treated with triphenylmethyl chloride (Tr-Cl) and K2CO3 in DMF to afford 2-[2-(tert-butoxycarbonylamino)thiazol-4-yl]-2(Z)-(triphenylmethoxyimino)acetic acid (III). The condensation of (III) with 7beta-amino-3-(methanesulfonyloxy)-3-cephem-4-carboxylic acid diphenylmethyl ester (IV) by means of phenylphosphoryl dichloride and N-methylmorpholine gives the 7beta-acetamido derivative (V), which is then condensed with 4-(acetylsulfanylmethylsulfanyl)-1-(triphenylmethyl)-1,2,3-triazole (VI) by means of NaOMe in THF/DMF/methanol to yield the fully protected compound (IX). Finally, this compound is deprotected by a treatment with AlCl3 anisole. The triazole (VI) can be obtained by reaction of the sodium salt of 1,2,3-triazole-4-thiol (VII) with thioacetic acid S-(chloromethyl)ester (VIII) in DMS followed by NH-protection with triphenylmethyl chloride.
| 【1】 Mealy, N.; Castaner, J.; S-1090. Drugs Fut 1996, 21, 3, 254. |
| 【2】 Takahashi, H.; Ide, Y. (Shionogi & Co. Ltd.); Triazolylthiomethylthio cephalosporin hydrochloride, its crystalline hydrate and the production of the same. EP 0581552; JP 1994092970; US 5407929 . |
| 【3】 Kubota, T.; Kume, M. (Shionogi & Co. Ltd.); Thioalkylthio cephalosporin derivs. EP 0467647; JP 1992234346; JP 1993059066; US 5214037 . |
| 【4】 Kume, M.; Kubota, T.; Kimura, Y.; Nakashimizu, H.; Motokawa, K.; Nakano, M.; Orally active cephalosporins. II. Synthesis and structure-activity relationships of new 7beta-[(Z)-2-(2-aminothiazol-4-yl)-2-hydroxyiminoacetamido]-cephalosporins with 1,2,3-triazole in C-3 side chain. J Antibiot 1993, 46, 1, 177-92. |
| 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) | 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 |
| (II) | 15890 | 2-[2-[(tert-butoxycarbonyl)amino]-1,3-thiazol-4-yl]-2-(hydroxyimino)acetic acid | C10H13N3O5S | 详情 | 详情 | |
| (III) | 15891 | 2-[2-[(tert-butoxycarbonyl)amino]-1,3-thiazol-4-yl]-2-[(trityloxy)imino]acetic acid | C29H27N3O5S | 详情 | 详情 | |
| (IV) | 15892 | benzhydryl (6R,7R)-7-amino-3-[[methyl(dimethylene)-lambda(6)-sulfanyl]oxy]-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate | C23H24N2O4S2 | 详情 | 详情 | |
| (V) | 15893 | benzhydryl (6R,7R)-7-([2-[2-[(tert-butoxycarbonyl)amino]-1,3-thiazol-4-yl]-2-[(trityloxy)imino]acetyl]amino)-3-[[methyl(dimethylene)-lambda(6)-sulfanyl]oxy]-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate | C52H49N5O8S3 | 详情 | 详情 | |
| (VI) | 15894 | S-[[(1-trityl-1H-1,2,3-triazol-4-yl)sulfanyl]methyl] ethanethioate | C24H21N3OS2 | 详情 | 详情 | |
| (VII) | 15895 | sodium 1H-1,2,3-triazole-4-thiolate | C2H2N3NaS | 详情 | 详情 | |
| (VIII) | 15896 | S-(chloromethyl) ethanethioate | C3H5ClOS | 详情 | 详情 | |
| (IX) | 15897 | benzhydryl (6R,7R)-7-([2-[2-[(tert-butoxycarbonyl)amino]-1,3-thiazol-4-yl]-2-[(trityloxy)imino]acetyl]amino)-8-oxo-3-([[(1-trityl-1H-1,2,3-triazol-4-yl)sulfanyl]methyl]sulfanyl)-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate | C71H60N8O7S4 | 详情 | 详情 |