5-[(1S,2S,3R,4S,7R,9S,10S,12R,15R,16S)-4,12-bis(acetoxy)-2-(benzoyloxy)-10,14,20,20-tetramethyl-11,18-dioxo-9-[(triethylsilyl)oxy]-6,17,19-trioxapentacyclo[11.6.1.0(1,16).0(3,10).0(4,7)]icos-13-en-15-yl] 3-(tert-butyl) (4S,5R)-2-(2,4-dimethoxyphenyl)-4-isobutyl-1,3-oxazolidine-3,5-dicarboxylate -Drug Synthesis Database

【结构式】

【分子编号】47539

【品名】5-[(1S,2S,3R,4S,7R,9S,10S,12R,15R,16S)-4,12-bis(acetoxy)-2-(benzoyloxy)-10,14,20,20-tetramethyl-11,18-dioxo-9-[(triethylsilyl)oxy]-6,17,19-trioxapentacyclo[11.6.1.0(1,16).0(3,10).0(4,7)]icos-13-en-15-yl] 3-(tert-butyl) (4S,5R)-2-(2,4-dimethoxyphenyl)-4-isobutyl-1,3-oxazolidine-3,5-dicarboxylate

【CA登记号】

【分子式】C₅₉H₇₉NO₁₉Si

【分子量】1134.3571

【元素组成】C 62.47% H 7.02% N 1.23% O 26.8% Si 2.48%

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：(XV)

Coupling reaction of the two synthons: (4S,5R)-3-(tert-Butoxycarbonyl)-2-(2,4-dimethoxyphenyl)-4-isobutyloxazolidine-5-carboxylic acid (XIV) was dissolved in methylene chloride and added to 7-O-(triethylsilyl)-14beta-hydroxybaccatin III-1,14-carbonate (IV) in toluene, in the presence of DMAP and DCC, to yield 7-O-(triethylsilyl)-14beta-hydroxybaccatin III-1,14-carbonate 13-[3-(tert-butoxycarbonyl)-2-(2,4-dimethoxyphenyl)-4-isobutyl-5-oxazolidinecarboxylate] (XV) (Scheme 26450201c). Deprotection reaction of the coupling product 7-O-(Triethylsilyl)-14beta-hydroxybaccatin III-1,14-carbonate 13-[3-(tert-butoxycarbonyl)-2-(2,4-dimethoxyphenyl)-4-isobutyl-5-oxazolidinecarboxylate] (XV) was dissolved in anhydrous methanol containing a catalytic amount of dry HCl at 0 C. After work-up and crystallization from ethanol/water, 13-[N-(tert-butoxycarbonyl)-b-isobutylisoserinyl]-14beta-hydroxybaccatin III-1,14-carbonate (BAY 59-8862) was obtained.

参考文献中间体

合成目标

【1】 Laccabue, D.; Pratesi, G.; BAY 59-8862. Drugs Fut 2001, 26, 6, 533.
【2】 Ojima, I.; Bombardelli, E. (Affymax Technologies, NV; State University of New York, Albany); Anti-tumor cpds., pharmaceutical compsns., methods for preparation thereof and for treatment. US 5705508 .

中间体序号	中间体编号	品名	分子式	供应商	用于合成
(IV)	19161	(1S,2S,3R,4S,7R,9S,10S,12R,15R,16S)-4,12-bis(acetoxy)-15-hydroxy-10,14,20,20-tetramethyl-11,18-dioxo-9-[(triethylsilyl)oxy]-6,17,19-trioxapentacyclo[11.6.1.0(1,16).0(3,10).0(4,7)]icos-13-en-2-yl benzoate	C₃₈H₅₀O₁₃Si	详情	详情
(XIV)	47538	(4S,5R)-3-(tert-butoxycarbonyl)-2-(2,4-dimethoxyphenyl)-4-isobutyl-1,3-oxazolidine-5-carboxylic acid	C₂₁H₃₁NO₇	详情	详情
(XV)	47539	5-[(1S,2S,3R,4S,7R,9S,10S,12R,15R,16S)-4,12-bis(acetoxy)-2-(benzoyloxy)-10,14,20,20-tetramethyl-11,18-dioxo-9-[(triethylsilyl)oxy]-6,17,19-trioxapentacyclo[11.6.1.0(1,16).0(3,10).0(4,7)]icos-13-en-15-yl] 3-(tert-butyl) (4S,5R)-2-(2,4-dimethoxyphenyl)-4-isobutyl-1,3-oxazolidine-3,5-dicarboxylate	C₅₉H₇₉NO₁₉Si	详情	详情

Extended Information