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【结 构 式】 
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【分子编号】34860 【品名】(1S,2S)-2-(4-[4-[4-(4-[[(3R,5R)-5-(2,4-difluorophenyl)-5-(1H-1,2,4-triazol-1-ylmethyl)tetrahydro-3-furanyl]methoxy]phenyl)-1-piperazinyl]phenyl]-5-oxo-4,5-dihydro-1H-1,2,4-triazol-1-yl)-1-methylbutyl 4-hydroxybutanoate 【CA登记号】 |
【 分 子 式 】C41H48F2N8O6 【 分 子 量 】786.8792464 【元素组成】C 62.58% H 6.15% F 4.83% N 14.24% O 12.2% |
合成路线1
该中间体在本合成路线中的序号：(XLVI)Sodium 4-hydroxybutyrate (XLII) was diben-zylated to give (XLIII), and then hydrolyzed with NaOH yielding 4-benzyl-oxybutyric acid (XLIV). Coupling of (XLIV) with alcohol (XXXII) then afforded ester (XLV). Deprotection of the benzyl ether of (XLV) by transfer hydrogenation with HCOOH and Pd catalyst produced hydroxy ester (XLVI). The precursor dibenzyl phosphate (XLI) was then obtained by coupling of (XLVI) with N,N-diisopropyl dibenzyl phosphoramidite, followed by oxidation of the intermediate phosphite with tertbutyl hydroperoxide. Finally, the hydrogenolysis of the benzyl groups of (XLI) as above furnished the title compound.
| 【1】 Bennett, F.; Girijavallabhan, V.M.; Patel, N.M.; Ganguly, A.; Saksena, A.K. (Schering Corp.); Tetrahydrofuran phosphate- and hydroxy esters, as prodrugs for the corresponding antifungal agent. EP 1027349; WO 9915522 . |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| 12912 | 1-(Bromomethyl)benzene; Alpha-bromotoluene | 100-39-0 | C7H7Br | 详情 | 详情 | |
| 40602 | C17H22NO3P | 详情 | 详情 | |||
| (XXXII) | 34850 | 4-[4-[4-(4-[[(3R,5R)-5-(2,4-difluorophenyl)-5-(1H-1,2,4-triazol-1-ylmethyl)tetrahydro-3-furanyl]methoxy]phenyl)-1-piperazinyl]phenyl]-2-[(1S,2S)-1-ethyl-2-hydroxypropyl]-2,4-dihydro-3H-1,2,4-triazol-3-one | C37H42F2N8O4 | 详情 | 详情 | |
| (XLI) | 34855 | (1S,2S)-2-(4-[4-[4-(4-[[(3R,5R)-5-(2,4-difluorophenyl)-5-(1H-1,2,4-triazol-1-ylmethyl)tetrahydro-3-furanyl]methoxy]phenyl)-1-piperazinyl]phenyl]-5-oxo-4,5-dihydro-1H-1,2,4-triazol-1-yl)-1-methylbutyl 4-[[bis(benzyloxy)phosphoryl]oxy]butanoate | C55H61F2N8O9P | 详情 | 详情 | |
| (XLII) | 34856 | sodium 4-hydroxybutanoate | 502-85-2 | C4H7NaO3 | 详情 | 详情 |
| (XLIII) | 34857 | benzyl 4-(benzyloxy)butanoate | C18H20O3 | 详情 | 详情 | |
| (XLIV) | 34858 | 4-(benzyloxy)butyric acid | C11H14O3 | 详情 | 详情 | |
| (XLV) | 34859 | (1S,2S)-2-(4-[4-[4-(4-[[(3R,5R)-5-(2,4-difluorophenyl)-5-(1H-1,2,4-triazol-1-ylmethyl)tetrahydro-3-furanyl]methoxy]phenyl)-1-piperazinyl]phenyl]-5-oxo-4,5-dihydro-1H-1,2,4-triazol-1-yl)-1-methylbutyl 4-(benzyloxy)butanoate | C48H54F2N8O6 | 详情 | 详情 | |
| (XLVI) | 34860 | (1S,2S)-2-(4-[4-[4-(4-[[(3R,5R)-5-(2,4-difluorophenyl)-5-(1H-1,2,4-triazol-1-ylmethyl)tetrahydro-3-furanyl]methoxy]phenyl)-1-piperazinyl]phenyl]-5-oxo-4,5-dihydro-1H-1,2,4-triazol-1-yl)-1-methylbutyl 4-hydroxybutanoate | C41H48F2N8O6 | 详情 | 详情 |