【结 构 式】 |
【分子编号】68934 【品名】(3-chloropyrazin-2-yl)(2-phenylquinolin-7-yl)methanol 【CA登记号】 |
【 分 子 式 】C20H14ClN3O 【 分 子 量 】347.803 【元素组成】C 69.07% H 4.06% Cl 10.19% N 12.08% O 4.60% |
合成路线1
该中间体在本合成路线中的序号:(XIX)Reduction of methyl 4-formyl-3-nitrobenzoate (XIII) by means of Fe and HCl in EtOH, followed by Friedländer condensation of the resulting aminoaldehyde with acetophenone (XIV) in the presence of KOH at 95 °C, and treatment with HCl, yields 2-phenylquinoline-7-carboxylic acid hydrochloride (XV). Reduction of acid (XV) with LiAlH4 in THF gives alcohol (XVI), which is then oxidized by means of MnO2 in CHCl3 to give 2-phenylquinoline-7-carbaldehyde (XVII). Coupling of carbaldehyde (XVII) with the metalated derivative of 2-chloropyrazine (XVIII) in the presence LTMP (prepared from BuLi and TMP) in THF yields the diaryl carbinol (XIX), which is then subjected to Mitsunobu reaction with phthalimide (XX) in the presence of PS-PPh3 and DIAD in THF to provide the N-substituted phthalimide (XXI). Hydrazinolysis of phthalimide (XXI) with NH2NH2 in EtOH/CH2Cl2 then affords amine (I).
Alternatively, carbaldehyde (XVII) can be prepared by arylation of 7-methylquinoline (XXII) with phenyl lithium in THF, followed by air oxidation to produce 7-methyl-2-phenylquinoline (XXIII). Side chain oxidation of (XXIII) using SeO2 at 160 °C provides the target aldehyde (XVII) .
【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 |
---|---|---|---|---|---|---|
(I) | 68918 | (3-chloropyrazin-2-yl)(2-phenylquinolin-7-yl)methanamine | C20H15ClN4 | 详情 | 详情 | |
(XIII) | 68930 | methyl 4-formyl-3-nitrobenzoate;4-Formyl-3-nitrobenzoicacid methyl ester | 153813-69-5 | C9H7NO5 | 详情 | 详情 |
(XIV) | 10317 | Acetophenone | 98-86-2 | C8H8O | 详情 | 详情 |
(XV) | 68931 | 2-phenylquinoline-7-carboxylic acid hydrochloride | C16H11NO2.HCl | 详情 | 详情 | |
(XVI) | 68932 | (2-phenylquinolin-7-yl)methanol | C16H13NO | 详情 | 详情 | |
(XVII) | 68933 | 2-phenylquinoline-7-carbaldehyde | C16H11NO | 详情 | 详情 | |
(XVIII) | 24075 | 2-chloropyrazine | 14508-49-7 | C4H3ClN2 | 详情 | 详情 |
(XIX) | 68934 | (3-chloropyrazin-2-yl)(2-phenylquinolin-7-yl)methanol | C20H14ClN3O | 详情 | 详情 | |
(XX) | 12376 | Phthalimide; 1H-Isoindole-1,3(2H)-dione; Isoindole-1,3-dione;Phthalic dicarboximide;Phenylimide;Isoindole-1,3-dione | 85-41-6 | C8H5NO2 | 详情 | 详情 |
(XXI) | 68935 | 2-((3-chloropyrazin-2-yl)(2-phenylquinolin-7-yl)methyl)isoindoline-1,3-dione | C28H17ClN4O2 | 详情 | 详情 | |
(XXII) | 68936 | 7-methylquinoline;m-Toluquinoline | 612-60-2 | C10H9N | 详情 | 详情 |
(XXIII) | 68937 | 7-methyl-2-phenylquinoline | 27356-39-4 | C16H13N | 详情 | 详情 |