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【结 构 式】

【分子编号】11557

【品名】2-[(1S,2S,3S,5S,6R,7E,10S,12S,13R,14S,16R)-6-allyl-5,13-bis[[tert-butyl(dimethyl)silyl]oxy]-12,14-dimethoxy-1-((E)-2-[(1R,3R,4R)-3-methoxy-4-[(triisopropylsilyl)oxy]cyclohexyl]-1-methylethenyl)-2,8,10,16-tetramethyl-17-oxo-3-[(triisopropylsilyl)oxy]-7-heptadecenyl] 1-(tert-butyl) (2S)-1,2-piperidinedicarboxylate

【CA登记号】

【 分 子 式 】C77H149NO12Si4

【 分 子 量 】1393.3716

【元素组成】C 66.37% H 10.78% N 1.01% O 13.78% Si 8.06%

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:(LVIII)

3) Coupling and cyclization process.- The condensation of the diphenylphosphine derivative (XXIV) with aldehyde (LI) by means of butyllithium in THF gives the hydroxy phosphine derivative (LII), which is treated with potassium hexamethyldisylazane (KHMDS) to afford dithiane (LIII). Partial desilylation of (LIII) with THF - water - trifluoroacetic acid gives alcohol (LIV), which is condensed with N-tert-butoxycarbonylpiperidine-2(S)-carboxylic acid (LV) by means of dicyclohexylcarbodiimide (DCC) and 4-(dimethylamino)pyridine in dichloromethane to yield the ester (LVI). Elimination of the dithiane ring of (LVI) with N-chlorosuccinimide and silver nitrate in anhydrous methanol affords the dimethyl acetal (LVII), which is hydrolyzed to the corresponding aldehyde (LVIII) with acetic acid. The condensation of (LVIII) with 4(S)-benzyl-3-[2-(4-methoxybenzyloxy)acetyl]oxazolidin-2-one (LIX) by means of dibutylboron trifluoromethylsulfonate in toluene gives the oxazolidone derivative (LX).

1 Jones, T.K.; Askin, D.; Mills, S.G.; Reamer, R.A.; Desmond, R.; Volante, R.P.; Tschaen, D.M.; Shinkai, I. (Merck & Co., Inc.); Process for synthesis of FK-506 and tricarbonyl intermediates. EP 0378318; JP 1990233643 .
中间体序号 中间体编号 品名 CAS号 分子式 供应商 用于合成
(XXIV) 11523 (3R,5S,6R,7S,9R)-6-[[tert-Butyl(dimethyl)silyl]oxy]-9-(1,3-dithian-2-yl)-5,7-dimethoxy-1,3-dimethyldecyl(diphenyl)phosphine oxide; [(3R,5S,6R,7S,9R)-6-[[tert-Butyl(dimethyl)silyl]oxy]-9-(1,3-dithian-2-yl)-5,7-dimethoxy-1,3-dimethyldecyl](oxo)diphenylphosphorane C36H59O4PS2Si 详情 详情
(LI) 11550 (2S,3S,5S,6S,7S,8E)-2-Allyl-3-[[tert-butyl(dimethyl)silyl]oxy]-9-[(1R,3R,4R)-3-methoxy-4-[(triisopropylsilyl)oxy]cyclohexyl]-6,8-dimethyl-7-[(triethylsilyl)oxy]-5-[(triisopropylsilyl)oxy]-8-nonenal C51H104O6Si4 详情 详情
(LII) 11553 (1E,3S,4S,5S,7S,8R,9E,12S,14S,15R,16S,18R)-8-Allyl-7,15-bis[[tert-butyl(dimethyl)silyl]oxy]-18-(1,3-dithian-2-yl)-14,16-dimethoxy-1-[(1R,3R,4R)-3-methoxy-4-[(triisopropylsilyl)oxy]cyclohexyl]-2,4,10,12-tetramethyl-5-[(triisopropylsilyl)oxy]-1,9-nonadecadien-3-ol C69H138O8S2Si4 详情 详情
(LIII) 11552 (5R,6S,8S,10E,12R,13S,15S,16S,17S)-12-Allyl-13-[[tert-butyl(dimethyl)silyl]oxy]-5-[(1S,3R)-3-(1,3-dithian-2-yl)-1-methoxybutyl]-19,19-diethyl-6-methoxy-17-((E)-2-[(1R,3R,4R)-3-methoxy-4-[(triisopropylsilyl)oxy]cyclohexyl]-1-methylethenyl)-2,2,3,3,8,10,16-heptamethyl-15-[(triisopropylsilyl)oxy]-4,18-dioxa-3,19-disila-10-henicosene; (1S,3S,4R,5E,8S,10S,11R,12S,14R)-4-Allyl-3,11-bis[[tert-butyl(dimethyl)silyl]oxy]-14-(1,3-dithian-2-yl)-10,12-dimethoxy-1-[(1S,2S,3E)-4-[(1R,3R,4R)-3-methoxy-4-[(triisopropylsilyl)oxy]cyclohexyl]-1,3-dimethyl-2-[(triethylsilyl)oxy]-3-butenyl]-6,8-dimethyl-5-pentadecenyl triisopropylsilyl ether C75H152O8S2Si5 详情 详情
(LIV) 11551 (5R,6S,8R,12R,13S,15S,16S,17S)-12-allyl-13-[[tert-butyl(dimethyl)silyl]oxy]-9-(diphenylphosphoryl)-5-[(1S,3R)-3-(1,3-dithian-2-yl)-1-methoxybutyl]-19,19-diethyl-6-methoxy-17-((E)-2-[(1R,3R,4R)-3-methoxy-4-[(triisopropylsilyl)oxy]cyclohexyl]-1-methyl C87H163O10PS2Si5 详情 详情
(LV) 11487 (2S)-1-(tert-Butoxycarbonyl)hexahydro-2-pyridinecarboxylic acid C11H19NO4 详情 详情
(LVI) 11555 2-[(1S,2S,3S,5S,6R,7E,10S,12S,13R,14S,16R)-6-allyl-5,13-bis[[tert-butyl(dimethyl)silyl]oxy]-16-(1,3-dithian-2-yl)-12,14-dimethoxy-1-((E)-2-[(1R,3R,4R)-3-methoxy-4-[(triisopropylsilyl)oxy]cyclohexyl]-1-methylethenyl)-2,8,10-trimethyl-3-[(triisopropylsilyl)oxy]-7-heptadecenyl] 1-(tert-butyl) (2S)-1,2-piperidinedicarboxylate C80H155NO11S2Si4 详情 详情
(LVII) 11556 2-[(1S,2S,3S,5S,6R,7E,10S,12S,13R,14S,16R)-6-allyl-5,13-bis[[tert-butyl(dimethyl)silyl]oxy]-12,14,17,17-tetramethoxy-1-((E)-2-[(1R,3R,4R)-3-methoxy-4-[(triisopropylsilyl)oxy]cyclohexyl]-1-methylethenyl)-2,8,10,16-tetramethyl-3-[(triisopropylsilyl)oxy]-7-heptadecenyl] 1-(tert-butyl) (2S)-1,2-piperidinedicarboxylate C79H155NO13Si4 详情 详情
(LVIII) 11557 2-[(1S,2S,3S,5S,6R,7E,10S,12S,13R,14S,16R)-6-allyl-5,13-bis[[tert-butyl(dimethyl)silyl]oxy]-12,14-dimethoxy-1-((E)-2-[(1R,3R,4R)-3-methoxy-4-[(triisopropylsilyl)oxy]cyclohexyl]-1-methylethenyl)-2,8,10,16-tetramethyl-17-oxo-3-[(triisopropylsilyl)oxy]-7-heptadecenyl] 1-(tert-butyl) (2S)-1,2-piperidinedicarboxylate C77H149NO12Si4 详情 详情
(LIX) 11558 (4S)-4-Benzyl-3-[3-(4-methoxyphenyl)propanoyl]-1,3-oxazolidin-2-one C20H21NO4 详情 详情
(LX) 11559 2-[(1S,2S,3S,5S,6R,7E,10S,12S,13R,14S,16R,17R)-6-allyl-19-[(4S)-4-benzyl-2-oxo-1,3-oxazolidin-3-yl]-5,13-bis[[tert-butyl(dimethyl)silyl]oxy]-17-hydroxy-12,14-dimethoxy-18-[(4-methoxybenzyl)oxy]-1-((E)-2-[(1R,3R,4R)-3-methoxy-4-[(triisopropylsilyl)oxy]cyclohexyl]-1-methylethenyl)-2,8,10,16-tetramethyl-19-oxo-3-[(triisopropylsilyl)oxy]-7-nonadecenyl] 1-(tert-butyl) (2S)-1,2-piperidinedicarboxylate C97H170N2O17Si4 详情 详情
Extended Information