(3aS,4R,7R,8S,9R,10R,11R,13R,15R,15aR)-10-[[(2S,3R,4S,6R)-3-(acetoxy)-4-(dimethylamino)-6-methyltetrahydro-2H-pyran-2-yl]oxy]-1-(4-chlorophenethyl)-4-ethyl-11-methoxy-3a,7,9,11,13,15-hexamethyl-2,6,14-trioxotetradecahydro-2H-oxacyclotetradecino[4,3-d][1,3]oxazol-8-yl 1H-imidazole-1-carboxylate -Drug Synthesis Database

【结构式】

【分子编号】38159

【品名】(3aS,4R,7R,8S,9R,10R,11R,13R,15R,15aR)-10-[[(2S,3R,4S,6R)-3-(acetoxy)-4-(dimethylamino)-6-methyltetrahydro-2H-pyran-2-yl]oxy]-1-(4-chlorophenethyl)-4-ethyl-11-methoxy-3a,7,9,11,13,15-hexamethyl-2,6,14-trioxotetradecahydro-2H-oxacyclotetradecino[4,3-d][1,3]oxazol-8-yl 1H-imidazole-1-carboxylate

【CA登记号】

【分子式】C₄₅H₆₅ClN₄O₁₂

【分子量】889.48356

【元素组成】C 60.77% H 7.37% Cl 3.99% N 6.3% O 21.58%

与该中间体有关的原料药合成路线共 2 条

合成路线1 合成路线2

合成路线1

该中间体在本合成路线中的序号：(VII)

Protection of 2'-O-acetyl-6-O-methylerythromycin A (I) with chlorotrimethylsilane afforded the 4''-O-trimethylsilyl derivative (II). Subsequent treatment with carbonyldiimidazole and NaH produced the dehydrated imidazolide (III), which was converted to the cyclic carbamate (V) upon reaction with 4-chlorophenethyl amine (IV). Acid hydrolysis of the cladinose moiety gave alcohol (VI), and further condensation with carbonyldiimidazole yielded imidazolide (VII).

参考文献中间体

合成目标

【1】 Waid, P.; Dalton, C.R.; Randolph, J.T.; Greer, J.; Nichols, C.J.; Haviv, F.; Mort, N.A.; Sauer, D.R. (Abbott Laboratories Inc.); Macrolide LHRH antagonists. WO 0012522 .

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)	38154	(2S,3R,4S,6R)-4-(dimethylamino)-2-[((3R,4S,5R,6R,7R,9R,11R,12R,13S,14R)-14-ethyl-12,13-dihydroxy-4-[[(4R,5S,6S)-5-hydroxy-4-methoxy-4,6-dimethyltetrahydro-2H-pyran-2-yl]oxy]-7-methoxy-3,5,7,9,11,13-hexamethyl-2,10-dioxooxacyclotetradecanyl)oxy]-6-methyltetrahydro-2H-pyran-3-yl acetate		C₄₀H₇₁NO₁₄	详情	详情
(II)	38155	(2S,3R,4S,6R)-4-(dimethylamino)-2-[[(3R,4S,5R,6R,7R,9R,11R,12R,13S,14R)-14-ethyl-12,13-dihydroxy-7-methoxy-4-([(4R,5S,6S)-4-methoxy-4,6-dimethyl-5-[(trimethylsilyl)oxy]tetrahydro-2H-pyran-2-yl]oxy)-3,5,7,9,11,13-hexamethyl-2,10-dioxooxacyclotetradecanyl]oxy]-6-methyltetrahydro-2H-pyran-3-yl acetate		C₄₃H₇₉NO₁₄Si	详情	详情
(III)	38156	(2R,3S,7R,9R,10R,11R,12S,13R)-10-[[(2S,3R,4S,6R)-3-(acetoxy)-4-(dimethylamino)-6-methyltetrahydro-2H-pyran-2-yl]oxy]-2-ethyl-9-methoxy-12-([(4R,5S,6S)-4-methoxy-4,6-dimethyl-5-[(trimethylsilyl)oxy]tetrahydro-2H-pyran-2-yl]oxy)-3,5,7,9,11,13-hexamethyl-6,14-dioxooxa-4-cyclotetradecen-3-yl 1H-imidazole-1-carboxylate		C₄₇H₇₉N₃O₁₄Si	详情	详情
(IV)	29459	4-chlorophenethylamine; 2-(4-chlorophenyl)-1-ethanamine	156-41-2	C₈H₁₀ClN	详情	详情
(V)	38157	(2S,3R,4S,6R)-2-[[(3aS,4R,7R,8S,9R,10R,11R,13R,15R,15aR)-1-(4-chlorophenethyl)-4-ethyl-11-methoxy-8-([(4R,5S,6S)-4-methoxy-4,6-dimethyl-5-[(trimethylsilyl)oxy]tetrahydro-2H-pyran-2-yl]oxy)-3a,7,9,11,13,15-hexamethyl-2,6,14-trioxotetradecahydro-2H-oxacyclotetradecino[4,3-d][1,3]oxazol-10-yl]oxy]-4-(dimethylamino)-6-methyltetrahydro-2H-pyran-3-yl acetate		C₅₂H₈₅ClN₂O₁₄Si	详情	详情
(VI)	38158	(2S,3R,4S,6R)-2-[[(3aS,4R,7R,8S,9S,10R,11R,13R,15R,15aR)-1-(4-chlorophenethyl)-4-ethyl-8-hydroxy-11-methoxy-3a,7,9,11,13,15-hexamethyl-2,6,14-trioxotetradecahydro-2H-oxacyclotetradecino[4,3-d][1,3]oxazol-10-yl]oxy]-4-(dimethylamino)-6-methyltetrahydro-2H-pyran-3-yl acetate		C₄₁H₆₃ClN₂O₁₁	详情	详情
(VII)	38159	(3aS,4R,7R,8S,9R,10R,11R,13R,15R,15aR)-10-[[(2S,3R,4S,6R)-3-(acetoxy)-4-(dimethylamino)-6-methyltetrahydro-2H-pyran-2-yl]oxy]-1-(4-chlorophenethyl)-4-ethyl-11-methoxy-3a,7,9,11,13,15-hexamethyl-2,6,14-trioxotetradecahydro-2H-oxacyclotetradecino[4,3-d][1,3]oxazol-8-yl 1H-imidazole-1-carboxylate		C₄₅H₆₅ClN₄O₁₂	详情	详情

合成路线2

该中间体在本合成路线中的序号：(VII)

Coupling of this imidazolide (VII) with the lithium salt of (S)-4-methyloxazolidine-2-one (VIII) at low temperature, followed by acid hydrolysis of the acetate ester furnished carbamate (IX). Mono-N-demethylation of (IX) to give secondary amine (X) was achieved by photochemical reaction with iodine and NaOAc. Finally, reductive alkylation with cyclopropanecarboxaldehyde (XI) in the presence of NaBH3CN produced the title cyclopropylmethylamino derivative.

参考文献中间体

合成目标

【1】 Waid, P.; Dalton, C.R.; Randolph, J.T.; Greer, J.; Nichols, C.J.; Haviv, F.; Mort, N.A.; Sauer, D.R. (Abbott Laboratories Inc.); Macrolide LHRH antagonists. WO 0012522 .

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)	38159	(3aS,4R,7R,8S,9R,10R,11R,13R,15R,15aR)-10-[[(2S,3R,4S,6R)-3-(acetoxy)-4-(dimethylamino)-6-methyltetrahydro-2H-pyran-2-yl]oxy]-1-(4-chlorophenethyl)-4-ethyl-11-methoxy-3a,7,9,11,13,15-hexamethyl-2,6,14-trioxotetradecahydro-2H-oxacyclotetradecino[4,3-d][1,3]oxazol-8-yl 1H-imidazole-1-carboxylate		C₄₅H₆₅ClN₄O₁₂	详情	详情
(VIII)	38160	(4S)-4-methyl-1,3-oxazolidin-2-one		C₄H₇NO₂	详情	详情
(IX)	38161			C₄₄H₆₆ClN₃O₁₃	详情	详情
(X)	38162			C₄₃H₆₄ClN₃O₁₃	详情	详情
(XI)	26463	cyclopropanecarbaldehyde	1489-69-6	C₄H₆O	详情	详情

Extended Information