【结 构 式】 |
【分子编号】57237 【品名】6-methoxy-4-methyl-2(1H)-quinolinone 【CA登记号】 |
【 分 子 式 】C11H11NO2 【 分 子 量 】189.21388 【元素组成】C 69.83% H 5.86% N 7.4% O 16.91% |
合成路线1
该中间体在本合成路线中的序号:(I)Chlorination of 6-methoxy-4-methylquinolin-2(1H)-one (I) with SO2Cl2 in hot acetic acid gives the 5-chloro derivative (II), which is nitrated with HNO3 in H2SO4 to yield the 8-nitroquinolinone (III). Condensation of compound (III) with 3-(trifluoromethyl)phenol (IV) by means of KOH in NMP provides the diaryl ether (V), which is treated with refluxing POCl3 to afford the 2-chloroquinoline (VI). Reaction of compound (VI) with MeONa in refluxing methanol results in the 2,6-dimethoxyquinoline derivative (VII), which is reduced with hydrazine over Pd/C to give the 8-aminoquinoline derivative (VIII). Condensation of aminoquinoline (VIII) with N-(4-iodopentyl)phthalimide (IX) by means of diisopropylamine in hot NMP yields the phthalimido precursor (X), which is finally cleaved with hydrazine in refluxing ethanol.
【1】 McIntyre, J.A.; Castaner, J.; Bayes, M.; Tafenoquine Succinate. Drugs Fut 2003, 28, 9, 859. |
【2】 Ugwuegbulam, C.O.; Foy, J.E. (GlaxoSmithKline Inc.; GlaxoSmithKline plc); Process for the preparation of anti-malarial drugs. US 6479660; WO 9713753 . |
【3】 LaMontagne, M.P.; et al.; Tricyclic compounds as selective muscarinic receptor antagonists. 3. Structure-selectivity relationships in a series of cardioselective (M2) antimuscarinics. J Med Chem 1989, 32, 8, 1728-32. |
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) | 57237 | 6-methoxy-4-methyl-2(1H)-quinolinone | C11H11NO2 | 详情 | 详情 | |
(II) | 57247 | 5-chloro-6-methoxy-4-methyl-2(1H)-quinolinone | C11H10ClNO2 | 详情 | 详情 | |
(III) | 57246 | 5-chloro-6-methoxy-4-methyl-8-nitro-2(1H)-quinolinone | C11H9ClN2O4 | 详情 | 详情 | |
(IV) | 33504 | 3-(trifluoromethyl)phenol | 98-17-9 | C7H5F3O | 详情 | 详情 |
(V) | 57245 | 6-methoxy-4-methyl-8-nitro-5-[3-(trifluoromethyl)phenoxy]-2(1H)-quinolinone | C18H13F3N2O5 | 详情 | 详情 | |
(VI) | 57244 | 2-chloro-6-methoxy-4-methyl-8-nitro-5-[3-(trifluoromethyl)phenoxy]quinoline; 2-chloro-6-methoxy-4-methyl-8-nitro-5-quinolinyl 3-(trifluoromethyl)phenyl ether | C18H12ClF3N2O4 | 详情 | 详情 | |
(VII) | 57243 | 2,6-dimethoxy-4-methyl-8-nitro-5-quinolinyl 3-(trifluoromethyl)phenyl ether; 2,6-dimethoxy-4-methyl-8-nitro-5-[3-(trifluoromethyl)phenoxy]quinoline | C19H15F3N2O5 | 详情 | 详情 | |
(VIII) | 48081 | 2,6-dimethoxy-4-methyl-5-[3-(trifluoromethyl)phenoxy]-8-quinolinamine; 2,6-dimethoxy-4-methyl-5-[3-(trifluoromethyl)phenoxy]-8-quinolinylamine | C19H17F3N2O3 | 详情 | 详情 | |
(IX) | 48082 | 2-(4-iodopentyl)-1H-isoindole-1,3(2H)-dione | C13H14INO2 | 详情 | 详情 | |
(X) | 48083 | 2-[4-([2,6-dimethoxy-4-methyl-5-[3-(trifluoromethyl)phenoxy]-8-quinolinyl]amino)pentyl]-1H-isoindole-1,3(2H)-dione | C32H30F3N3O5 | 详情 | 详情 |