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【结 构 式】

【分子编号】25427

【品名】4-ethyl-1,2,3,4-tetrahydroquinoline

【CA登记号】

【 分 子 式 】C11H15N

【 分 子 量 】161.24684

【元素组成】C 81.94% H 9.38% N 8.69%

与该中间体有关的原料药合成路线共 1 条

合成路线1

该中间体在本合成路线中的序号:(VII)

The intermediate 4-ethyltetrahydroquinoline (VII) has been prepared by two procedures: 1.- Conjugate addition of acrylic acid (II) to aniline (I) gave 3-(phenylamino)propionic acid (III), which was cyclized with PPA at 100 C to afford quinolinone (IV). After protection of (IV) as the tert-butyl carbamate (V), addition of ethylmagnesium bromide provided carbinol (VI). Hydrogenolysis of the hydroxyl group of (VI), followed by deprotection with trifluoroacetic acid then furnished tetrahydroquinoline (VII). 2.- In an alternative procedure, side-chain alkylation of lepidine (VIII) with CH3I and LDA provided 4-ethylquinoline (IX). This was then reduced to the desired tetrahydroquinoline (VII) using NaBH4 and NiCl2. 3.- After nitration of (VII) with HNO3 and H2SO4, the resulting 7-nitroquinoline (X) was reduced to diamine (XI) by catalytic hydrogenation over Pd/C. Finally, Knorr cyclization of (XI) with ethyl 4,4,4-trifluoroacetylacetate (XII) and ZnCl2 produced the target pyridoquinoline.

1 Hamann, L.G.; Mani, N.S.; Davis, R.L.; Marschke, K.B.; Wang, X.-N.; Jones, T.K.; Discovery of a potent, orally active, nonsteroidal androgen receptor agonist: 4-Ethyl-1,2,3,4-tetrahydro-6-(trifluoromethyl)-8-pyridono[5,6-g]quinoline (LG121071). J Med Chem 1999, 42, 2, 210.
2 Jones, T.K.; Goldman, M.E.; Pooley, C.L.F.; Winn, D.T.; Edwards, J.E.; West, S.J.; Tegley, C.M.; Zhi, L.; Hamann, L.G.; Farmer, L.J.; Davis, R.J. (Ligand Pharmaceuticals, Inc.); Steroid receptor modulator cpds. and methods. EP 0800519; JP 1998510840; US 5688808; US 5688810; US 5693646; US 5693647; US 5696127; US 5696130; US 5696133; WO 9619458 .
3 Edwards, J.P.; Higuchi, R.; Jones, T. (Ligand Pharmaceuticals, Inc.); Androgen receptor modulator cpds. and methods. EP 0918774; US 6017924; WO 9749709 .
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) 12294 Aniline; Phenylamine 62-53-3 C6H7N 详情 详情
(II) 19139 acrylic acid 79-10-7 C3H4O2 详情 详情
(III) 25423 3-anilinopropionic acid 5652-38-0 C9H11NO2 详情 详情
(IV) 25424 2,3-dihydro-4(1H)-quinolinone 4295-36-7 C9H9NO 详情 详情
(V) 25425 tert-butyl 4-oxo-3,4-dihydro-1(2H)-quinolinecarboxylate C14H17NO3 详情 详情
(VI) 25426 tert-butyl 4-ethyl-4-hydroxy-3,4-dihydro-1(2H)-quinolinecarboxylate C16H23NO3 详情 详情
(VII) 25427 4-ethyl-1,2,3,4-tetrahydroquinoline C11H15N 详情 详情
(VIII) 25428 4-methylquinoline 491-35-0 C10H9N 详情 详情
(IX) 25429 4-ethylquinoline C11H11N 详情 详情
(X) 25430 4-ethyl-7-nitro-1,2,3,4-tetrahydroquinoline C11H14N2O2 详情 详情
(XI) 25431 4-ethyl-1,2,3,4-tetrahydro-7-quinolinamine; 4-ethyl-1,2,3,4-tetrahydro-7-quinolinylamine C11H16N2 详情 详情
(XII) 25432 ethyl 4,4,4-trifluoro-3-oxobutanoate 372-31-6 C6H7F3O3 详情 详情
Extended Information