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【结 构 式】 
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【分子编号】60304 【品名】1-[8-(2,4-dichlorophenyl)-2-methyl-4-quinolinyl]-4-hydroxy-4-piperidinecarbonitrile 【CA登记号】 |
【 分 子 式 】C22H19Cl2N3O 【 分 子 量 】412.31788 【元素组成】C 64.09% H 4.64% Cl 17.2% N 10.19% O 3.88% |
合成路线1
该中间体在本合成路线中的序号：(VI)Alternatively, hydroxyquinoline (I) is chlorinated in refluxing POCl3 to provide chloroquinoline (II). Substitution of (II) with 4-piperidone ethylene ketal (III) in boiling DMF furnishes the piperidinyl quinoline derivative (IV), which is further hydrolyzed to piperidone (V) under acidic conditions. Addition of cyanide to piperidone (V) gives rise to cyanohydrin (VI), and subsequent dehydration by means of POCl3/pyridine affords the unsaturated nitrile (VII). Finally, partial hydrolysis of nitrile (VII) with HCl in formic acid leads to the target amide compound
| 【1】 Kameo, K.; Kumagai, T.; Nakazato, A.; Okubo, T. (Taisho Pharmaceutical Co., Ltd.); Tetrahydropyridino or piperidino heterocyclic derivs.. EP 1299378; WO 0202549 . |
| 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) | 60297 | 8-(2,4-dichlorophenyl)-2-methyl-4-quinolinol | C16H11Cl2NO | 详情 | 详情 | |
| (II) | 60301 | 4-chloro-8-(2,4-dichlorophenyl)-2-methylquinoline | C16H10Cl3N | 详情 | 详情 | |
| (III) | 11338 | 1,4-Dioxa-8-azaspiro[4.5]decane; 4-Piperidone ethylene ketal | 177-11-7 | C7H13NO2 | 详情 | 详情 |
| (IV) | 60302 | 8-(2,4-dichlorophenyl)-4-(1,4-dioxa-8-azaspiro[4.5]dec-8-yl)-2-methylquinoline | C23H22Cl2N2O2 | 详情 | 详情 | |
| (V) | 60303 | 1-[8-(2,4-dichlorophenyl)-2-methyl-4-quinolinyl]-4-piperidinone | C21H18Cl2N2O | 详情 | 详情 | |
| (VI) | 60304 | 1-[8-(2,4-dichlorophenyl)-2-methyl-4-quinolinyl]-4-hydroxy-4-piperidinecarbonitrile | C22H19Cl2N3O | 详情 | 详情 | |
| (VII) | 60305 | 1-[8-(2,4-dichlorophenyl)-2-methyl-4-quinolinyl]-1,2,3,6-tetrahydro-4-pyridinecarbonitrile | C22H17Cl2N3 | 详情 | 详情 |