3-烯丙基-2,4-二氯-6,7-二甲氧基喹啉的合成研究
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摘要
以3,4-二甲氧基苯胺和丙二酸为原料,在三氯氧磷作用下合成2,4-二氯-6,7-二甲氧基喹啉,2,4-二氯-6,7-二甲氧基喹啉在二异丙基氨基锂作用下与3-溴丙烯发生SNAr反应得到3-烯丙基-2,4-二氯-6,7-二甲氧基喹啉. 2步反应总收率为66. 1%.产物结构经~1H NMR和ESI-MS确证.通过对反应条件研究确定最佳反应工艺,在该最佳反应工艺条件下2,4-二氯-6,7-二甲氧基-3-(2-甲基烯丙基)喹啉的合成收率为77. 5%. 3-烯丙基-2,4-二氯-6,7-二甲氧基喹啉经过还原、氧化、取代反应得到3-(3-叔丁基二甲基硅氧丙基)-2,4-二氯-6,7-二甲氧基喹啉,3步反应总收率为42. 8%.
3-Allyl-2,4-dichloro-6,7-dimethoxyquinoline is synthesized by an efficient and practical method from 3,4-dimethoxyaniline and malonic acid,through two steps in a total yield of 66. 1%,involving 2,4-dichloro-6,7-dimethoxyquinoline forming in the presence of POCl3,then SNAr reaction of 2,4-dichloro-6,7-dimethoxyquinoline with 3-bromoprop-1-ene in the presence of lithium diisopropylamide. The structure of the intermediate and product are confirmed by1 H NMR and ESI-MS. The optimal reaction conditions are investigated. Also,2,4-dichloro-6,7-dimethoxy-3-( 2-methylallyl) quinoline is obtained by the optimal reaction process in a yield of 77. 5%. The synthetic application of 3-allyl-2,4-dichloro-6,7-dimethoxyquinoline is also investigated. 3-( 3-(( tert-butyldimethylsilyl) oxy)propyl)-2,4-dichloro-6,7-dimethoxyquinoline is synthesized in a yield of 42. 8% from title compound through reduction,oxidation and substitution reaction.
3-Allyl-2,4-dichloro-6,7-dimethoxyquinoline is synthesized by an efficient and practical method from 3,4-dimethoxyaniline and malonic acid,through two steps in a total yield of 66. 1%,involving 2,4-dichloro-6,7-dimethoxyquinoline forming in the presence of POCl3,then SNAr reaction of 2,4-dichloro-6,7-dimethoxyquinoline with 3-bromoprop-1-ene in the presence of lithium diisopropylamide. The structure of the intermediate and product are confirmed by1 H NMR and ESI-MS. The optimal reaction conditions are investigated. Also,2,4-dichloro-6,7-dimethoxy-3-( 2-methylallyl) quinoline is obtained by the optimal reaction process in a yield of 77. 5%. The synthetic application of 3-allyl-2,4-dichloro-6,7-dimethoxyquinoline is also investigated. 3-( 3-(( tert-butyldimethylsilyl) oxy)propyl)-2,4-dichloro-6,7-dimethoxyquinoline is synthesized in a yield of 42. 8% from title compound through reduction,oxidation and substitution reaction.
引文
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[4]Nielsen O H,Ahnfelt-Rnne I,Elmgreen J.A comparison of the effect of timegadine,levamisole,and D-penicillamine on human neutrophil metabolism of endogenous arachidonic acid and chemotaxis[J].Basic and Clinical Pharmacology and Toxicology,2010,62(5):322-325.
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[6]Smith R A,Stokes E C,Langdon-Jones E E,et al.Cyclometalated cinchophen ligands on iridium(iii):towards water-soluble complexes with visible luminescence[J].Dalton Transactions,2013,42(28):10347-10357.
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[12]Eskens F A L M,de Jonge M J A,Bhargava P,et al.Biologic and clinical activity of tivozanib(AV-951,KRN-951),a selective inhibitor of VEGF receptor-1,-2,and-3tyrosine kinases,in a 4-week-on,2-week-off schedule in patients with advanced solid tumors[J].Clinical Cancer Research,2011,17(22):7156-7163.