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【结 构 式】 
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【分子编号】48080 【品名】2-chloro-6-methoxy-4-methyl-5-[3-(trifluoromethyl)phenoxy]-8-quinolinamine; 2-chloro-6-methoxy-4-methyl-5-[3-(trifluoromethyl)phenoxy]-8-quinolinylamine 【CA登记号】 |
【 分 子 式 】C18H14ClF3N2O2 【 分 子 量 】382.7693496 【元素组成】C 56.48% H 3.69% Cl 9.26% F 14.89% N 7.32% O 8.36% |
合成路线1
该中间体在本合成路线中的序号：(XX)Reaction of 8-amino-6-methoxy-4-methyl-5-[3-(trifluoromethyl)phenoxy]quinoline (XIV) with phthalic anhydride (XV) affords the phthalimido derivative (XVI), which is oxidized with MCPBA to yield the quinoline N-oxide (XVII). Treatment of compound (XVII) with neutral alumina gives the quinolone derivative (XVIII), which by reaction with POCl3 in refluxing CHCl3 provides the 2-chloroquinoline derivative (XIX). Alternatively, reaction of the quinoline N-oxide (XVII) with POCl3 as before also gives the 2-chloroquinoline derivative (XIX) The removal of the phthalimido group of compound (XIX) by means of hydrazine in refluxing ethanol gives the chlorinated aminoquinoline (XX), which is finally treated with MeONa in hot DMF.
| 【1】 McIntyre, J.A.; Castaner, J.; Bayes, M.; Tafenoquine Succinate. Drugs Fut 2003, 28, 9, 859. |
| 【2】 LaMontagne, M.P.; Blumbergs, P. (Department of the Army); 4-Methyl-5-(unsubstd. and substd. phenoxy)-2,6-dimethoxy-8-(aminoalkylamino)quinolines. US 4617394 . |
| 【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 |
|---|---|---|---|---|---|---|
| (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 | |
| (XIV) | 48075 | 6-methoxy-4-methyl-5-[3-(trifluoromethyl)phenoxy]-8-quinolinylamine; 6-methoxy-4-methyl-5-[3-(trifluoromethyl)phenoxy]-8-quinolinamine | C18H15F3N2O2 | 详情 | 详情 | |
| (XV) | 11900 | 2-Benzofuran-1,3-dione;1,2-Benzenedicarboxylic Anhydride;1,2-BENZENE DICARBOXYLIC ACID ANHYDRIDE;1,2-BENZENEDICARBONIC ACID, ANHYDRIDE;1,3-DIOXOPHTHALAN;1,3-ISOBENZOFURANDIONE;o-phthalic anhydride; Phthalic anhydride | 85-44-9 | C8H4O3 | 详情 | 详情 |
| (XVI) | 48076 | 2-[6-methoxy-4-methyl-5-[3-(trifluoromethyl)phenoxy]-8-quinolinyl]-1H-isoindole-1,3(2H)-dione | C26H17F3N2O4 | 详情 | 详情 | |
| (XVII) | 48077 | 8-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)-6-methoxy-4-methyl-5-[3-(trifluoromethyl)phenoxy]-1-quinoliniumolate | C26H17F3N2O5 | 详情 | 详情 | |
| (XVIII) | 48078 | 2-[6-methoxy-4-methyl-2-oxo-5-[3-(trifluoromethyl)phenoxy]-1,2-dihydro-8-quinolinyl]-1H-isoindole-1,3(2H)-dione | C26H17F3N2O5 | 详情 | 详情 | |
| (XIX) | 48079 | 2-[2-chloro-6-methoxy-4-methyl-5-[3-(trifluoromethyl)phenoxy]-8-quinolinyl]-1H-isoindole-1,3(2H)-dione | C26H16ClF3N2O4 | 详情 | 详情 | |
| (XX) | 48080 | 2-chloro-6-methoxy-4-methyl-5-[3-(trifluoromethyl)phenoxy]-8-quinolinamine; 2-chloro-6-methoxy-4-methyl-5-[3-(trifluoromethyl)phenoxy]-8-quinolinylamine | C18H14ClF3N2O2 | 详情 | 详情 |