新型3-(4-氟-苯基)-4(3H)-嘧啶酮-5-甲酸乙酯衍生物的合成
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摘要
以4-氟苯基硫脲和乙氧基甲叉基丙二酸二乙酯(DEMM)为起始原料,通过环合、烷基化、氧化、水解、加成、威廉姆逊醚合成等一系列反应,合成了7个2-位具有不同取代基团的标题化合物。其结构经1HNMR、13CNMR和ESI-MS表征。
A series of seven ethyl-3-( 4-fluorophenyl)-4( 3H)-pyrimidinone-5-carboxylates with varying substituents at the 2-position was synthesized from( 4-fluorophenyl) thiourea and diethyl ethoxymethylene malonate via a sequence of reactions including cyclization,alkylation,oxidation,hydrolysis,addition and Williamson ether synthesis. The structures were confirmed by1 HNMR,13CNMR and ESI-MS.
A series of seven ethyl-3-( 4-fluorophenyl)-4( 3H)-pyrimidinone-5-carboxylates with varying substituents at the 2-position was synthesized from( 4-fluorophenyl) thiourea and diethyl ethoxymethylene malonate via a sequence of reactions including cyclization,alkylation,oxidation,hydrolysis,addition and Williamson ether synthesis. The structures were confirmed by1 HNMR,13CNMR and ESI-MS.
引文
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[2]BARTMLI O J,ANGUITA L M.Method for preparing pyrimidone derivatives with antifungal activity:US,2 003064 986A1[P].2003-04-03.
[3]MURAGLA E,KINZD O D,GARDELL C,et al.Design and synthesis of bieychc pyrimidinones as potent and oraly bioavailable HIV-1 integrase inhibitors[J].J.Med.Chem.,2008,51(4):861-874.
[4]ERNEST L B.The mode of action of RH-1965:a new phenylpyrimidinone bleaching herbicide[J].Pest Manag.Sci.,2000,56(27):245-248.
[5]袁丹,容如滨,喻宗沅.嘧啶类化合物的研究进展[J].化学与生物工程,2008,25(6):13-17.
[6]DANDU R,HUDKINS R L,JOSEF K A,et al.Uracil derivatives as AXL and c-MET kinase inhibitors:US,2 015210 670A1[P].2015-07-30.
[7]BOTSI S,TSOLOMITIS A.One or two step acid mediated cyclocondensation process for the preparation of 5-carbethoxy-2-thiouracils from diethyl ethoxymethylenemalonate and thioureas[J].Heterocycl.Commun.,2007,13(4):229-234.
[8]GROSJEAN S,TRIKI S,MESLIN J,et al.Synthesis of nitrogen bicyclic scaffolds:pyrimido[1,2-a]pyrimidine-2,6-diones[J].Tetrahedron,2010,66(52):9 912-9 924.
[9]PARLATOM C,MUGNAINI C,RENZULLI M L,et al.Solid phase synthesis of 5,6-disubstituted pyrimidinone and pyrimidindione derivatives[J].Arkivoc,2004,(5):349-363.
[10]TIBILETTI F,SIMONETTI M,PENONI A,et al.Onepot synthesis of meridianins and meridianin analogues via indolization of nitrosoarenes[J].Tetrahedron,2010,66(6):1 280-1 288.
[11]MAI A,ARTICO M,RAGNO R,et al.5-Alkyl-2-alkylamino-6-(2,6-difluorophenylalkyl)-3,4-dihy-dropyrimidin-4(3H)-ones,a new series of potent,broad-spectrum non-nucleoside reverse trans-criptaseinhibitors belonging to the DABO family[J].Bioorg.Med.Chem.,2005,13(6):2 065-2 077.