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【结 构 式】 
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【药物名称】ME-1036, CP-5609 【化学名称】(1R,5S,6S)-2-[7-[1-(Carbamoylmethyl)pyridin-1-ium-3-ylcarbonyl]imidazo[5,1-b]thiazol-2-yl]-6-[1(R)-hydroxyethyl]-1-methyl-1-carba-2-penem-3-carboxylate 【CA登记号】 【 分 子 式 】C23H21N5O6S 【 分 子 量 】495.51772 |
【开发单位】Meiji Seika (Originator) 【药理作用】Antibiotics, ANTIINFECTIVE THERAPY, Carbapenems |
合成路线1
Metalation of 7-iodoimidazo[5,1-b]thiazole (I) with ethylmagnesium bromide, followed by addition to 3-pyridinecarboxaldehyde (II) provides carbinol (III), which is further oxidized to ketone (IV) by means of MnO2. Lithiation of (IV) and further treatment with chlorotributyltin affords the stannyl derivative (V). The carbapenem ketone (VI) is converted into the vinyl triflate (VII) upon treatment with trifluoromethanesulfonic anhydride and diisopropyl ethylamine. Then, Stille coupling between vinyl triflate (VII) and the stannyl derivative (V) gives rise to the imidazothiazolyl carbapenem (VIII). Quaternization of the pyridine ring of (VIII) with iodoacetamide furnishes the pyridinium salt (IX). Finally the p-nitrobenzyl ester group of (IX) is removed by hydrogenolysis over Pd/C to provide the title compound
| 【1】 Shitara, E.; Yamamoto, Y.; Kano, Y.; Maruyama, T.; Takahashi, M.; Atsumi, K.; CP5609, a novel parenteral carbapenem: Synthesis and structure-activity relationships. 42nd Intersci Conf Antimicrob Agents Chemother (Sept 27 2002, San Diego) 2002, Abst F-319. |
| 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) | 47193 | 7-iodoimidazo[5,1-b][1,3]thiazole | C5H3IN2S | 详情 | 详情 | |
| (II) | 12849 | Nicotinaldehyde; 3-Pyridinecarboxaldehyde | 500-22-1 | C6H5NO | 详情 | 详情 |
| (III) | 62675 | imidazo[5,1-b][1,3]thiazol-7-yl(3-pyridinyl)methanol | C11H9N3OS | 详情 | 详情 | |
| (IV) | 62676 | imidazo[5,1-b][1,3]thiazol-7-yl(3-pyridinyl)methanone | C11H7N3OS | 详情 | 详情 | |
| (V) | 62677 | 3-pyridinyl[2-(tributylstannyl)imidazo[5,1-b][1,3]thiazol-7-yl]methanone | C23H33N3OSSn | 详情 | 详情 | |
| (VI) | 22575 | 4-nitrobenzyl (2R,5R,6S)-6-[(1R)-1-hydroxyethyl]-4-methyl-3,7-dioxo-1-azabicyclo[3.2.0]heptane-2-carboxylate | C17H18N2O7 | 详情 | 详情 | |
| (VII) | 38750 | 4-nitrobenzyl (4R,5R,6S)-6-[(1R)-1-hydroxyethyl]-4-methyl-7-oxo-3-[[(trifluoromethyl)sulfonyl]oxy]-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylate | C18H17F3N2O9S | 详情 | 详情 | |
| (VIII) | 62678 | 4-nitrobenzyl (4S,5R,6S)-6-[(1R)-1-hydroxyethyl]-4-methyl-7-oxo-3-[7-(3-pyridinylcarbonyl)imidazo[5,1-b][1,3]thiazol-2-yl]-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylate | C28H23N5O7S | 详情 | 详情 | |
| (IX) | 62679 | 1-(2-amino-2-oxoethyl)-3-{[2-((4S,5R,6S)-6-[(1R)-1-hydroxyethyl]-4-methyl-2-{[(4-nitrobenzyl)oxy]carbonyl}-7-oxo-1-azabicyclo[3.2.0]hept-2-en-3-yl)imidazo[5,1-b][1,3]thiazol-7-yl]carbonyl}pyridinium iodide | C30H27IN6O8S | 详情 | 详情 |