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【结 构 式】 
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【药物名称】 【化学名称】N-(Cyclopropylmethyl)-N-[2-methyl-8-(2,4,6-trimethylphenyl)quinolin-4-yl]-N-propylamine 【CA登记号】 【 分 子 式 】C26H32N2 【 分 子 量 】372.55834 |
【开发单位】Janssen (Originator), Neurocrine Biosciences (Originator) 【药理作用】Antidepressants, Anxiolytics, Mood Disorders, Treatment of, PSYCHOPHARMACOLOGIC DRUGS, CRF1 Antagonists |
合成路线1
Suzuki coupling of 2-bromoaniline (I) with boronic acid (II) in the presence of a palladium catalyst gave biphenyl (III). Subsequent condensation of (III) with ethyl acetoacetate (IV) afforded enamine (V), which was cyclized to hydroxyquinoline (VI) in refluxing diphenyl ether. Chlorination of (VI) in boiling POCl3 produced the corresponding 4-chloroquinoline (VII). This was finally condensed with N-(cyclopropylmethyl)-N--propylamine (VIII) to provide the target aminoquinoline.
| 【1】 Huang, C.; Chen, C.; McCarthy, J.R.; Haddach, M.; Wilcoxen, K.M. (Janssen Pharmaceutica NV; Neurocrine Biosciences Inc.); CRF antagonistic quino- and quinazolines. EP 0977737; WO 9847874 . |
| 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) | 27739 | 2-bromoaniline | 615-36-1 | C6H6BrN | 详情 | 详情 |
| (II) | 27740 | mesitylboronic acid | 5980-97-2 | C9H13BO2 | 详情 | 详情 |
| (III) | 27741 | 2',4',6'-trimethyl[1,1'-biphenyl]-2-amine | C15H17N | 详情 | 详情 | |
| (IV) | 11819 | ethyl acetoacetate; ethyl 3-oxobutanoate；Acetoacetic ester;Ethyl beta-ketobutyrate;ethyl 3-oxobutyrate | 141-97-9 | C6H10O3 | 详情 | 详情 |
| (V) | 27742 | ethyl (E)-3-(2-mesitylanilino)-2-butenoate | C21H25NO2 | 详情 | 详情 | |
| (VI) | 27743 | 8-mesityl-2-methyl-4-quinolinol | C19H19NO | 详情 | 详情 | |
| (VII) | 27744 | 4-chloro-8-mesityl-2-methylquinoline | C19H18ClN | 详情 | 详情 | |
| (VIII) | 27745 | N-(cyclopropylmethyl)-1-propanamine | 26389-60-6 | C7H15N | 详情 | 详情 |