【结 构 式】 |
【分子编号】61341 【品名】6-(3-(1-adamantyl)-4-{[tert-butyl(dimethyl)silyl]oxy}phenyl)nicotinaldehyde 【CA登记号】 |
【 分 子 式 】C28H37NO2Si 【 分 子 量 】447.69282 【元素组成】C 75.12% H 8.33% N 3.13% O 7.15% Si 6.27% |
合成路线1
该中间体在本合成路线中的序号:(VII)Coupling between 4-bromophenol (I) and 1-adamantanol (II) in the presence of H2SO4 affords the adamantanyl phenol (III), which is further protected as the silyl ether (IV) by means of t-butyldimethylsilyl chloride and DMAP. Addition of triisopropyl borate to the organolithium derivative of (IV) gives rise, after aqueous quenching, to the boronic acid (V). Then, Suzuki coupling of boronic acid (V) with 6-bromopyridine-3-carbaldehyde (VI) furnishes the phenylpyridine adduct (VII). Desilylation of (VII) to provide phenol (VIII) is accomplished by treatment with tetrabutylammonium fluoride in THF. Finally, condensation of pyridine aldehyde (VIII) with 2,4-thiazolidinedione (IX) under Knoevenagel conditions provides the target compound
【1】 Spruce, L.W.; Pfahl, M.; Fanjul, A.; Tachdjian, C.; Al-Shamma, H.A.; Pleynet, D.P.M.; Wiemann, T.R.; Ibarra, J.B. (Maxia Pharmaceuticals, Inc.); Heterocyclic derivs. for the treatment of cancer and other proliferative diseases. WO 02/072009 . |
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) | 25313 | 4-bromophenol | 106-41-2 | C6H5BrO | 详情 | 详情 |
(II) | 52642 | 1-Adamantanol; 1-Hydroxyadamantane; Tricyclo[3.3.1.1]decan-1-ol | 768-95-6 | C10H16O | 详情 | 详情 |
(III) | 59536 | 2-(1-adamantyl)-4-bromophenol | C16H19BrO | 详情 | 详情 | |
(IV) | 59537 | 1-(5-bromo-2-methoxyphenyl)adamantane; 2-(1-adamantyl)-4-bromophenyl methyl ether | C17H21BrO | 详情 | 详情 | |
(V) | 61340 | 3-(1-adamantyl)-4-{[tert-butyl(dimethyl)silyl]oxy}phenylboronic acid | C22H35BO3Si | 详情 | 详情 | |
(VI) | 61343 | 6-bromonicotinaldehyde | C6H4BrNO | 详情 | 详情 | |
(VII) | 61341 | 6-(3-(1-adamantyl)-4-{[tert-butyl(dimethyl)silyl]oxy}phenyl)nicotinaldehyde | C28H37NO2Si | 详情 | 详情 | |
(VIII) | 61342 | 6-[3-(1-adamantyl)-4-hydroxyphenyl]nicotinaldehyde | C22H23NO2 | 详情 | 详情 | |
(IX) | 10883 | 1,3-Thiazolane-2,4-dione; 2,4-Thiazolidinedione | 2295-31-0 | C3H3NO2S | 详情 | 详情 |