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【结 构 式】 
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【分子编号】68939 【品名】7-chloro-2-phenylquinoline 【CA登记号】 |
【 分 子 式 】C15H10ClN 【 分 子 量 】239.70384 【元素组成】C 75.16% H 4.2% Cl 14.79% N 5.84% |
合成路线1
该中间体在本合成路线中的序号：(XXVI)In one method, oxidation of 4-chloro-2-nitrotoluene (XXIV) with NaIO4 in the presence of DMFA in DMF at 135 °C yields 4-chloro-2-nitrobenzaldehyde (XXV). Reduction of the nitro group in compound (XXV) with Fe and HCl in EtOH/H2O, followed by Friedländer condensation of the resulting aminoaldehyde with acetophenone (XIV) using KOH at reflux gives 7-chloro-2-phenylquinoline (XXVI). Miyaura borylation of chloroquinoline (XXVI) with bis(pinacolato)diboron (XXVII) in the presence of 1,3-bis(2,6-diisopropylphenyl)imidazolium chloride [IPr·HCl], Pd(OAc)2 and KOAc in refluxing THF furnishes boronate ester (XI).
In another method, arylation of 7-quinolinol (XXVIII) using phenyl lithium in THF, optionally after protection of the hydroxyl group with TBDMSCl in the presence of DMAP and Et3N in CH2Cl2, leads to 2-phenyl-7-quinolinol (XXIX). Quinolinol (XXIX) is then activated by Tf2O in pyr/CH2Cl2 to produce the aryl triflate (XXX), which condenses with bis(pinacolato)diboron (XXVII) in the presence of PdCl2(dppf) CH2Cl2, dppf and KOAc in 1,4-dioxane to afford the dioxaborolane derivative (XI) .
| 【1】 Arnold, L.D., Cesario, C., Coate, H. et al. (OSI Pharmaceuticals, Inc.). 6,6-Bicyclic ring substituted heterobicyclic protein kinase inhibitors. EP 1740591, EP 2168968, EP 2305682, EP 2308879, JP 2007531754, JP 2009197013, US 200635031, WO 005097800. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (XI) | 68928 | 2-phenyl-7-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)quinoline | C21H22BNO2 | 详情 | 详情 | |
| (XIV) | 10317 | Acetophenone | 98-86-2 | C8H8O | 详情 | 详情 |
| (XXIV) | 41485 | 4-chloro-1-methyl-2-nitrobenzene；4-chloro-2-nitrotoluene;4-chloro-1-methyl-2-nitro-benzene | 89-59-8 | C7H6ClNO2 | 详情 | 详情 |
| (XXV) | 68938 | 4-chloro-2-nitrobenzaldehyde;2-Nitro-4-chlorobenzaldehyde | 5551-11-1 | C7H4ClNO3 | 详情 | 详情 |
| (XXVI) | 68939 | 7-chloro-2-phenylquinoline | C15H10ClN | 详情 | 详情 | |
| (XXVII) | 53342 | 4,4,4',4',5,5,5',5'-Octamethyl-2,2'-bi-1,3,2-dioxaborolane; Bis(pinacolato)diboron; Diboron pinacol ester | 73183-34-3 | C12H24B2O4 | 详情 | 详情 |
| (XXVIII) | 68940 | quinolin-7-ol | C9H7NO | 详情 | 详情 | |
| (XXIX) | 68941 | 2-phenyl-7-quinolinol;2-phenylquinolin-7-ol | C15H11NO | 详情 | 详情 | |
| (XXX) | 68942 | 2-phenylquinolin-7-yl trifluoromethanesulfonate | C16H10F3NO3S | 详情 | 详情 |