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【结 构 式】 
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【分子编号】62308 【品名】(2S,3R,4S,6R)-2-[((3aS,4R,7S,9R,10R,11S,13R,15R,15aR)-7-fluoro-3a,7,9,11,13,15-hexamethyl-11-{[(E)-3-[1,8]naphthyridin-3-yl-2-propenyl]oxy}-2,6,8,14-tetraoxo-4-propyltetradecahydro-2H-oxacyclotetradecino[4,3-d][1,3]oxazol-10-yl)oxy]-4-(dimethylamino 【CA登记号】 |
【 分 子 式 】C49H63FN4O11 【 分 子 量 】903.0579832 【元素组成】C 65.17% H 7.03% F 2.1% N 6.2% O 19.49% |
合成路线1
该中间体在本合成路线中的序号：(XXVIII)Elimination of the mesylate group of (XXIII) utilizing DBU in acetone leads to the 10,11-anhydro ketolide (XXIV). Acylation of (XXIV) with carbonyl diimidazole and NaH, followed by treatment with ammonium hydroxide gives rise to the 11,12-cyclic carbamate (XXV). Subsequent Heck coupling of allyl ether (XXV) with 3-bromo-1,8-naphthyridine (XXVI) leads to the (naphthyridinyl)propenyl derivative (XXVII). Then, fluorination of (XXVII) with N-fluorobenzenesulfonimide furnishes the 2-fluoro ketolide (XXVIII). Finally, the benzoate ester group of (XXVIII) is removed in refluxing MeOH to provide the title compound.
| 【1】 Macielag, M.; Abbanat, D.; Ashley, G.; Foleno, B.; Fu, H.; Li, Y.; Wira, E.; Bush, K.; Structure-activity studies of 15-methyl ketolides: Optimization of the heterocyclic substituent. 42nd Intersci Conf Antimicrob Agents Chemother (Sept 27 2002, San Diego) 2002, Abst F-1662. |
| 【2】 Hlasta, D.; Khosla, C.; Chu, D.T.W.; Ashley, G.; Henninger, T.C.; Grant, E.B. (Ortho-McNeil Pharmaceutical, Inc.); Ketolide antibacterials. WO 0232918 . |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (XXIII) | 62303 | (2S,3R,4S,6R)-2-({(3R,5R,6R,7S,9R,11R,12R,13R,14R)-7-(allyloxy)-13-hydroxy-3,5,7,9,11,13-hexamethyl-12-[(methylsulfonyl)oxy]-2,4,10-trioxo-14-propyloxacyclotetradecanyl}oxy)-4-(dimethylamino)-6-methyltetrahydro-2H-pyran-3-yl benzoate | C41H63NO13S | 详情 | 详情 | |
| (XXIV) | 62304 | (2S,3R,4S,6R)-2-{[(3R,5R,6R,7S,9R,13S,14R)-7-(allyloxy)-13-hydroxy-3,5,7,9,11,13-hexamethyl-2,4,10-trioxo-14-propyloxa-11-cyclotetradecen-6-yl]oxy}-4-(dimethylamino)-6-methyltetrahydro-2H-pyran-3-yl benzoate | C40H59NO10 | 详情 | 详情 | |
| (XXV) | 62305 | (2S,3R,4S,6R)-2-{[(3aS,4R,7R,9R,10R,11S,13R,15R,15aR)-11-(allyloxy)-3a,7,9,11,13,15-hexamethyl-2,6,8,14-tetraoxo-4-propyltetradecahydro-2H-oxacyclotetradecino[4,3-d][1,3]oxazol-10-yl]oxy}-4-(dimethylamino)-6-methyltetrahydro-2H-pyran-3-yl benzoate | C41H60N2O11 | 详情 | 详情 | |
| (XXVI) | 62306 | 3-bromo[1,8]naphthyridine | C8H5BrN2 | 详情 | 详情 | |
| (XXVII) | 62307 | (2S,3R,4S,6R)-2-[((3aS,4R,7R,9R,10R,11S,13R,15R,15aR)-3a,7,9,11,13,15-hexamethyl-11-{[(E)-3-[1,8]naphthyridin-3-yl-2-propenyl]oxy}-2,6,8,14-tetraoxo-4-propyltetradecahydro-2H-oxacyclotetradecino[4,3-d][1,3]oxazol-10-yl)oxy]-4-(dimethylamino)-6-methy | C49H64N4O11 | 详情 | 详情 | |
| (XXVIII) | 62308 | (2S,3R,4S,6R)-2-[((3aS,4R,7S,9R,10R,11S,13R,15R,15aR)-7-fluoro-3a,7,9,11,13,15-hexamethyl-11-{[(E)-3-[1,8]naphthyridin-3-yl-2-propenyl]oxy}-2,6,8,14-tetraoxo-4-propyltetradecahydro-2H-oxacyclotetradecino[4,3-d][1,3]oxazol-10-yl)oxy]-4-(dimethylamino | C49H63FN4O11 | 详情 | 详情 |