【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% |
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 |