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【结 构 式】 
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【分子编号】59659 【品名】(2S,3R,4S,6R)-2-[((3aS,4R,7R,9R,10R,11S,13R,15R,15aR)-4-ethyl-3a,7,9,11,13,15-hexamethyl-2,6,8,14-tetraoxo-11-{[3-(3-quinolinyl)-2-propynyl]oxy}tetradecahydro-2H-oxacyclotetradecino[4,3-d][1,3]oxazol-10-yl)oxy]-4-(dimethylamino)-6-methyltetrahydro-2H-pyran-3-yl acetate 【CA登记号】 |
【 分 子 式 】C44H59N3O11 【 分 子 量 】805.96608 【元素组成】C 65.57% H 7.38% N 5.21% O 21.84% |
合成路线1
该中间体在本合成路线中的序号：(XII)Conversion of imidazolide (VII) into the cyclic carbamate (VIII) was carried out employing liquid ammonia in cold acetonitrile. The 3-cladinose moiety of (VIII) was then selectively removed by smooth acidic hydrolysis, yielding (IX). Subsequent oxidation of the 3-hydroxyl group of (IX) by means of N-chlorsuccinimide in the presence of dimethyl sulfide led to the ketolide compound (X). Palladium-catalyzed coupling of 3-bromoquinoline (XI) to the terminal acetylenic position of (X) furnished (XII). The title compound was finally obtained by methanolysis of the 2'-acetate group of (XII) at room temperature.
| 【1】 Or, Y.S.; Nilius, A.M.; Chu, D.T.W.; Zhang, X.; Wang, S.; Clark, R.F.; Ma, Z.; Structure-activity relationships leading to the discovery of A-217213, a novel 6-O-substituted ketolide with excellent activity against drug-resistant pathogens. 41st Intersci Conf Antimicrob Agents Chemother (Dec 16 2001, Chicago) 2001, Abst F-1171. |
| 【2】 Or, Y.S.; Ma, Z.; Clark, R.F.; Chu, D.T.; Plattner, J.J. (Abbott Laboratories Inc.); 6-O-Substd. ketolides having antibacterial activity. EP 0929563; US 5866549; WO 9809978 . |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (VII) | 59655 | (2R,3S,7R,9S,10R,11R,12S,13R)-10-{[(2S,3R,4S,6R)-3-(acetyloxy)-4-(dimethylamino)-6-methyltetrahydro-2H-pyran-2-yl]oxy}-12-{[(2R,4R,5S,6S)-5-(acetyloxy)-4-methoxy-4,6-dimethyltetrahydro-2H-pyran-2-yl]oxy}-2-ethyl-3,5,7,9,11,13-hexamethyl-6,14-dioxo-9-(2-propynyloxy)oxa-4-cyclotetradecen-3-yl 1H-imidazole-1-carboxylate | C48H73N3O15 | 详情 | 详情 | |
| (VIII) | 59656 | (2S,3S,4R,6R)-6-{[(3aS,4R,7R,8S,9R,10R,11S,13R,15R,15aR)-10-{[(2S,3R,4S,6R)-3-(acetyloxy)-4-(dimethylamino)-6-methyltetrahydro-2H-pyran-2-yl]oxy}-4-ethyl-3a,7,9,11,13,15-hexamethyl-2,6,14-trioxo-11-(2-propynyloxy)tetradecahydro-2H-oxacyclotetradecino[4,3-d][1,3]oxazol-8-yl]oxy}-4-methoxy-2,4-dimethyltetrahydro-2H-pyran-3-yl acetate | C45H72N2O15 | 详情 | 详情 | |
| (IX) | 59657 | (2S,3R,4S,6R)-2-{[(3aS,4R,7R,8R,9S,10R,11S,13R,15R,15aR)-4-ethyl-8-hydroxy-3a,7,9,11,13,15-hexamethyl-2,6,14-trioxo-11-(2-propynyloxy)tetradecahydro-2H-oxacyclotetradecino[4,3-d][1,3]oxazol-10-yl]oxy}-4-(dimethylamino)-6-methyltetrahydro-2H-pyran-3-yl acetate | C35H56N2O11 | 详情 | 详情 | |
| (X) | 59658 | (2S,3R,4S,6R)-2-{[(3aS,4R,7R,9R,10R,11S,13R,15R,15aR)-4-ethyl-3a,7,9,11,13,15-hexamethyl-2,6,8,14-tetraoxo-11-(2-propynyloxy)tetradecahydro-2H-oxacyclotetradecino[4,3-d][1,3]oxazol-10-yl]oxy}-4-(dimethylamino)-6-methyltetrahydro-2H-pyran-3-yl acetate | C35H54N2O11 | 详情 | 详情 | |
| (XI) | 28432 | 3-bromoquinoline | 5332-24-1 | C9H6BrN | 详情 | 详情 |
| (XII) | 59659 | (2S,3R,4S,6R)-2-[((3aS,4R,7R,9R,10R,11S,13R,15R,15aR)-4-ethyl-3a,7,9,11,13,15-hexamethyl-2,6,8,14-tetraoxo-11-{[3-(3-quinolinyl)-2-propynyl]oxy}tetradecahydro-2H-oxacyclotetradecino[4,3-d][1,3]oxazol-10-yl)oxy]-4-(dimethylamino)-6-methyltetrahydro-2H-pyran-3-yl acetate | C44H59N3O11 | 详情 | 详情 |