(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 -Drug Synthesis Database

【结构式】

【分子编号】59656

【品名】(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

【CA登记号】

【分子式】C₄₅H₇₂N₂O₁₅

【分子量】881.07116

【元素组成】C 61.35% H 8.24% N 3.18% O 27.24%

与该中间体有关的原料药合成路线共 1 条

合成路线1

该中间体在本合成路线中的序号：(VIII)

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.

参考文献中间体

合成目标

【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

Extended Information