|
【结 构 式】 
|
【分子编号】16539 【品名】tert-butyl(dimethyl)silyl (1S)-1-[3-[(E)-2-(7-chloro-2-quinolinyl)ethenyl]phenyl]-3-[2-[1-methyl-1-(tetrahydro-2H-pyran-2-yloxy)ethyl]phenyl]propyl ether; 2-[(E)-2-[3-((1S)-1-[[tert-butyl(dimethyl)silyl]oxy]-3-[2-[1-methyl-1-(tetrahydro-2H-pyran-2-yloxy)ethyl]phenyl]propyl)phenyl]ethenyl]-7-chloroquinoline 【CA登记号】 |
【 分 子 式 】C40H50ClNO3Si 【 分 子 量 】656.38014 【元素组成】C 73.2% H 7.68% Cl 5.4% N 2.13% O 7.31% Si 4.28% |
合成路线1
该中间体在本合成路线中的序号：(XVII)The selective silylation of the diol (VII) with tert-butyldimethylsilyl chloride (TBDMS-Cl)/dimethylaminopyridine (DMAP) and imidazole in dichloromethane gives the monosilylated compound (XVI), which is treated with dihydropyran and triphenylphosphonium bromide to yield (XVII) with the tertiary alcohol protected as its tetrahydropyranyl ether. The desilylation of (XVII) with tetrabutylammonium fluoride (TBAF) in THF affords the secondary alcohol (XVIII), which is mesylated as usual giving the mesylate (XIX).
| 【1】 Labelle, M.; Belley, M.; Gareau, Y.; et al.; Discovery of MK-0476, a potent and orally active leukotriene D4 receptor antagonist devoid of peroxisomal enzyme induction. Bioorg Med Chem Lett 1995, 5, 3, 283-8. |
| 【2】 Graul, A.; Martín, L.; Castañer, J.; Montelukast Sodium. Drugs Fut 1997, 22, 10, 1103. |
| 【3】 Bhupathy, M.; McNamara, J.M.; Sidler, D.R.; Volante, R.P.; Bergan, J.J. (Merck & Co., Inc.); Process for the preparation of leukotriene antagonists. WO 9518107 . |
| 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) | 16529 | (1S)-1-[3-[(E)-2-(7-chloro-2-quinolinyl)ethenyl]phenyl]-3-[2-(1-hydroxy-1-methylethyl)phenyl]-1-propanol | C29H28ClNO2 | 详情 | 详情 | |
| (XVI) | 16538 | 2-[2-((3S)-3-[[tert-butyl(dimethyl)silyl]oxy]-3-[3-[(E)-2-(7-chloro-2-quinolinyl)ethenyl]phenyl]propyl)phenyl]-2-propanol | C35H42ClNO2Si | 详情 | 详情 | |
| (XVII) | 16539 | tert-butyl(dimethyl)silyl (1S)-1-[3-[(E)-2-(7-chloro-2-quinolinyl)ethenyl]phenyl]-3-[2-[1-methyl-1-(tetrahydro-2H-pyran-2-yloxy)ethyl]phenyl]propyl ether; 2-[(E)-2-[3-((1S)-1-[[tert-butyl(dimethyl)silyl]oxy]-3-[2-[1-methyl-1-(tetrahydro-2H-pyran-2-yloxy)ethyl]phenyl]propyl)phenyl]ethenyl]-7-chloroquinoline | C40H50ClNO3Si | 详情 | 详情 | |
| (XVIII) | 16540 | (1S)-1-[3-[(E)-2-(7-chloro-2-quinolinyl)ethenyl]phenyl]-3-[2-[1-methyl-1-(tetrahydro-2H-pyran-2-yloxy)ethyl]phenyl]-1-propanol | C34H36ClNO3 | 详情 | 详情 | |
| (XIX) | 16541 | (1S)-1-[3-[(E)-2-(7-chloro-2-quinolinyl)ethenyl]phenyl]-3-[2-[1-methyl-1-(tetrahydro-2H-pyran-2-yloxy)ethyl]phenyl]propyl methanesulfonate | C35H38ClNO5S | 详情 | 详情 |