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【结 构 式】 
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【分子编号】23861 【品名】3,4-dihydro-1(2H)-quinolinylamine; 3,4-dihydro-1(2H)-quinolinamine 【CA登记号】 |
【 分 子 式 】C9H12N2 【 分 子 量 】148.20776 【元素组成】C 72.94% H 8.16% N 18.9% |
合成路线1
该中间体在本合成路线中的序号：(V)The reaction of 1-indanone (I) with sodium azide in acetic acid/sulfuric acid gives the tetrahydroquinolone (II), which is reduced with LiAlH4 in THF, yielding the tetrahydroquinoline (III). The reaction of (III) with NaNO2 and sulfuric acid afords the N-nitroso derivative (IV), which is reduced wiith LiAlH4 in THF to the N-amino compound (V). The reaction of (V) with cyclohexane-1,3-dione (VI) gives the monohydrazone (VII), which is cyclized by means of HCl in refluxing acetic acid, yielding the tetracyclic compound (VIII). The reaction of (VIII) with dimethylamine and paraformaldehyde in hot acetic acid provides compound (IX), which is treated with 2-methylimidazole (X) in refluxing water to afford racemic cilansetron (XI). Finally, this racemate is submitted to optical resolution with di-p-toluyl-D-tartaric acid or D-pyroglutamic acid.
| 【1】 Castaner, J.; Rabasseda, X.; Silvestre, J.S.; Graul, A.; Cilansetron. Drugs Fut 1999, 24, 5, 475. |
| 【2】 Haeck, H.H.; Hamminga, D.; Van Wijngaarden, I.; Wouters, W. (Duphar International Research BV); New anellated indole derivs.. AU 8818414; EP 0297651; JP 1989022870; US 4939136 . |
| 【3】 Verbeek, J.-M.; Van der Meij, P.F.C. (Duphar International Research BV); Process for the preparation of enantiomerically pure imidazolyl cpds.. EP 0768309 . |
| 【4】 de Jonge, A.; Tulp, M.T.M.; Olivier, B.; Tipker, J.; van Hes, R.; Mol, F.; Hamminga, D.; Standaar, P.J.; Van Wijngaarden, I.; Development of high-affinity 5-HT3 receptor antagonists. Structure-affinity relationships of novel 1,7-annelated indole derivatives. 1. J Med Chem 1993, 36, 23, 3693. |
| 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) | 23857 | 1-indanone | 83-33-0 | C9H8O | 详情 | 详情 |
| (II) | 18553 | 3,4-dihydro-2(1H)-quinolinone | 553-03-7 | C9H9NO | 详情 | 详情 |
| (III) | 23859 | 1,2,3,4-tetrahydroquinoline | 635-46-1 | C9H11N | 详情 | 详情 |
| (IV) | 23860 | 1-nitroso-1,2,3,4-tetrahydroquinoline | C9H10N2O | 详情 | 详情 | |
| (V) | 23861 | 3,4-dihydro-1(2H)-quinolinylamine; 3,4-dihydro-1(2H)-quinolinamine | C9H12N2 | 详情 | 详情 | |
| (VI) | 11244 | 1,3-Cyclohexanedione | 504-02-9 | C6H8O2 | 详情 | 详情 |
| (VII) | 23863 | 3-[3,4-dihydro-1(2H)-quinolinylimino]cyclohexanone | C15H18N2O | 详情 | 详情 | |
| (VIII) | 23864 | 5,6,9,10-tetrahydro-4H-pyrido[3,2,1-jk]carbazol-11(8H)-one | C15H15NO | 详情 | 详情 | |
| (IX) | 23865 | 10-[(dimethylamino)methyl]-5,6,9,10-tetrahydro-4H-pyrido[3,2,1-jk]carbazol-11(8H)-one | C18H22N2O | 详情 | 详情 | |
| (X) | 15670 | 2-Methylimidazole; 2-Methyl-1H-imidazole | 693-98-1 | C4H6N2 | 详情 | 详情 |
| (XI) | 23867 | 10-[(2-methyl-1H-imidazol-1-yl)methyl]-5,6,9,10-tetrahydro-4H-pyrido[3,2,1-jk]carbazol-11(8H)-one | C20H21N3O | 详情 | 详情 |