(3R,4S,5R,6R,7R,9R,12R,13S,14R)-6-[[(2S,3R,4S,6R)-4-(dimethylamino)-3-hydroxy-6-methyltetrahydro-2H-pyran-2-yl]oxy]-7,12,13-trihydroxy-4-[[(2R,4R,5S,6S)-5-hydroxy-4-methoxy-4,6-dimethyltetrahydro-2H-pyran-2-yl]oxy]-3,5,7,9,11,13,14-heptamethyl-2,10-oxacyclotetradecanedione 10-oxime -Drug Synthesis Database

【结构式】

【分子编号】45908

【品名】(3R,4S,5R,6R,7R,9R,12R,13S,14R)-6-[[(2S,3R,4S,6R)-4-(dimethylamino)-3-hydroxy-6-methyltetrahydro-2H-pyran-2-yl]oxy]-7,12,13-trihydroxy-4-[[(2R,4R,5S,6S)-5-hydroxy-4-methoxy-4,6-dimethyltetrahydro-2H-pyran-2-yl]oxy]-3,5,7,9,11,13,14-heptamethyl-2,10-oxacyclotetradecanedione 10-oxime

【CA登记号】

【分子式】C₃₆H₆₆N₂O₁₃

【分子量】734.92572

【元素组成】C 58.84% H 9.05% N 3.81% O 28.3%

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：(II)

Treatment of erythromycin derivative (I) with hydroxylamine in isopropanol in the presence of HOAc affords oxime (II), which is then converted into the isopropoxycyclohexyl oxime form (IV) by reaction with 1,1-diisopropoxycyclohexane (III) and p-toluensulfonate (PPTS) in CH2Cl2. Regioselective protection of (IV) by means of N-(trimethylsilyl)-imidazole (Me3Si-Im) and chlorotrimethylsilane (TMSCl) in CH2Cl2 yields derivative (V), which is then converted into derivative (VI) by first methylation with methyl bromide and KOtBu in THF/methyl sulfoxide followed by deprotection with HOAc in acetonitrile. Oxime (VI) is then treated with sodium hydrosulfite (Na2S2O4) and formic acid in EtOH/H2O to provide derivative (VII).

参考文献中间体

合成目标

【1】 Chu, D.; Grant, E.; Hlasta, D.; Henninger, T.; Khosla, C. (Kosan Biosciences, Inc.; Ortho-McNeil Pharmaceutical, Inc.); Ketolide antibacterials. WO 0062783 .

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)	45907	(3R,4S,5R,6R,7R,9R,12R,13S,14R)-6-[[(2S,3R,4S,6R)-4-(dimethylamino)-3-hydroxy-6-methyltetrahydro-2H-pyran-2-yl]oxy]-7,12,13-trihydroxy-4-[[(2R,4R,5S,6S)-5-hydroxy-4-methoxy-4,6-dimethyltetrahydro-2H-pyran-2-yl]oxy]-3,5,7,9,11,13,14-heptamethyl-2,10-oxacyclotetradecanedione		C₃₆H₆₅NO₁₃	详情	详情
(II)	45908	(3R,4S,5R,6R,7R,9R,12R,13S,14R)-6-[[(2S,3R,4S,6R)-4-(dimethylamino)-3-hydroxy-6-methyltetrahydro-2H-pyran-2-yl]oxy]-7,12,13-trihydroxy-4-[[(2R,4R,5S,6S)-5-hydroxy-4-methoxy-4,6-dimethyltetrahydro-2H-pyran-2-yl]oxy]-3,5,7,9,11,13,14-heptamethyl-2,10-oxacyclotetradecanedione 10-oxime		C₃₆H₆₆N₂O₁₃	详情	详情
(III)	45909	1-isopropoxycyclohexyl isopropyl ether; 1,1-diisopropoxycyclohexane	1132-95-2	C₁₂H₂₄O₂	详情	详情
(IV)	45910	(3R,4S,5R,6R,7R,9R,12R,13S,14R)-6-[[(2S,3R,4S,6R)-4-(dimethylamino)-3-hydroxy-6-methyltetrahydro-2H-pyran-2-yl]oxy]-7,12,13-trihydroxy-4-[[(2R,4R,5S,6S)-5-hydroxy-4-methoxy-4,6-dimethyltetrahydro-2H-pyran-2-yl]oxy]-3,5,7,9,11,13,14-heptamethyl-2,10-oxacyclotetradecanedione 10-[O-(1-isopropoxycyclohexyl)oxime]		C₄₅H₈₂N₂O₁₄	详情	详情
(V)	45911	(3R,4S,5R,6R,7R,9R,12R,13S,14R)-6-([(2S,3R,4S,6R)-4-(dimethylamino)-6-methyl-3-[(trimethylsilyl)oxy]tetrahydro-2H-pyran-2-yl]oxy)-7,12,13-trihydroxy-4-([(2R,4R,5S,6S)-4-methoxy-4,6-dimethyl-5-[(trimethylsilyl)oxy]tetrahydro-2H-pyran-2-yl]oxy)-3,5,7,9,11,13,14-heptamethyl-2,10-oxacyclotetradecanedione 10-[O-(1-isopropoxycyclohexyl)oxime]		C₅₁H₉₈N₂O₁₄Si₂	详情	详情
(VI)	45912	(3R,4S,5R,6R,7R,9R,12R,13S,14R)-6-[[(2S,3R,4S,6R)-4-(dimethylamino)-3-hydroxy-6-methyltetrahydro-2H-pyran-2-yl]oxy]-12,13-dihydroxy-4-[[(2R,4R,5S,6S)-5-hydroxy-4-methoxy-4,6-dimethyltetrahydro-2H-pyran-2-yl]oxy]-7-methoxy-3,5,7,9,11,13,14-heptamethyl-2,10-oxacyclotetradecanedione 10-oxime		C₃₇H₆₈N₂O₁₃	详情	详情
(VII)	45913	(3R,4S,5R,6R,7R,9R,12R,13S,14R)-6-[[(2S,3R,4S,6R)-4-(dimethylamino)-3-hydroxy-6-methyltetrahydro-2H-pyran-2-yl]oxy]-12,13-dihydroxy-4-[[(2R,4R,5S,6S)-5-hydroxy-4-methoxy-4,6-dimethyltetrahydro-2H-pyran-2-yl]oxy]-7-methoxy-3,5,7,9,11,13,14-heptamethyl-2,10-oxacyclotetradecanedione		C₃₇H₆₇NO₁₃	详情	详情

Extended Information