2-芳基取代的吡啶并[2,3-d]嘧啶衍生物的合成
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摘要
以2-氨基-3-氰基吡啶为起始原料,先制备得到3-氨甲基吡啶-2-胺,在氯化亚铜、三乙烯二胺和2,2,6,6-四甲基-1-哌啶氧催化体系下,得到几种2-芳基取代的吡啶并[2,3-d]嘧啶衍生物。同时考察了反应温度、反应溶剂、反应时间对反应收率的影响。该方法具有操作简便,后处理简单、反应收率高的特点。目标化合物结构均经1HNMR、13CNMR和LCMS确证。
Using 2-amino-3-cyanylpyridine as starting material,the 3-aminomethylene-2-amine was first prepared. Several 2-aryl substituted pyridio [2,3-d] pyrimidine derivatives were designed and synthesized,by using Cu Cl/DABCO/TEMPO as the catalysts.The effects of reaction temperature,solvent and time on reaction yield were also investigated.This method has the advantages of simple operation,simple post-treatment and high reaction rate. The structures of the compounds were confirmed by1 HNMR、13 CNMR and LC-MS.
Using 2-amino-3-cyanylpyridine as starting material,the 3-aminomethylene-2-amine was first prepared. Several 2-aryl substituted pyridio [2,3-d] pyrimidine derivatives were designed and synthesized,by using Cu Cl/DABCO/TEMPO as the catalysts.The effects of reaction temperature,solvent and time on reaction yield were also investigated.This method has the advantages of simple operation,simple post-treatment and high reaction rate. The structures of the compounds were confirmed by1 HNMR、13 CNMR and LC-MS.
引文
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[14]罗维,徐运启,苑丽红,等.2-(2-吡啶)-5,6,7,8-四氢吡啶并[4,3-d]嘧啶及其衍生物的合成[J].化学试剂,2017,39(2):191-194.
[15]黄志斌,刘学成,胡明华,等.吡啶并[2,3-d]嘧啶衍生物受体的合成及对阴离子识别研究[J].有机化学,2014,34(2):382-386.
[16]RIADI Y,GEESI M.Photochemical route for the synthesis of novel 2-mono substituted pyrido[2,3-d]pyrimidines by palladium-catalyzed cross-coupling reactions[J].Chem.Pap.,2018,72(3):697-701.
[2]PAUL B,LEE E E.3-Aminoquinazolin-2,4-dione antibacterial agents:WO 0 153 273[P].2001-07-26.
[3]ELDER J T,VARANI J.Compositions containing retinoids and erb inhibitors and their use in inhibiting retinoid skin damage:NZ 516 873[P].2003-11-28.
[4]NAKAYAMA K,KAWATO H,WATANABE J,et al.MexAB-OprM specific efflux pump inhibitors in Pseudomonas aeruginosa. Part 3:optimization of potency in the pyridopyrimidine series through the application of a pharmacophore model[J].Bioorg.Med.Chem.Lett.,2004,14(2):475-479.
[5]VEACH D R,BORNMANN W,CLARKSON B D,et al.Pyridopyrimidine kinse inhibitors:WO 2 004 063 195[P].2004-07-29.
[6]PALANKI M S S,SUTO M.Pyridopyrimidine analogs and related compounds and methods for treating inflammatory conditions:US 6 150 372[P].2000-11-21.
[7]ROBERTON A D,JACKSON S. Therapeutic morpholinosubstituted compounds:WO 0 153 266[P].2001-07-26.
[8]HECKLER R E,JOURDAN G P. Condensed pyrimidine derivates:EP 414 386[P].1991-02-27.
[9]HOSMANE R S,LIM B B,SUMMERS M F. Rearrangements in heterocyclic synthesis.2.novel transformations of2-aminonicotinonitrile and anthranilonitrile[J]. Cheminform,1989,20(18):5 309-5 315.
[10]CHAN J,BRUKE B J,BAUCOM K,et al.Practical syntheses of a CXCR3 antagonist[J]. J. Org. Chem.,2011,76(6):1 767-1 774.
[11]XU C,JIA F C,ZHOU Z W,et al.Copper-catalyzed multicomponent domino reaction of 2-bromoaldehydes,benzylamines,and sodium azide for the assembly of quinazoline derivatives[J]. J. Org. Chem.,2016,81(7):3 000-3 006.
[12]邓兰青,钟宏,王帅.2,4-二氨基喹唑啉和2,4-二氨基吡啶并[2,3-d]嘧啶衍生物的合成[J].有机化学,2014,34(2):414-418.
[13]HAN B,YANG X L,WANG C,et al.Cu Cl/DABCO/4-HO-TEMPO-catalyzed aerobic oxidative synthesis of 2-substituted quinazolines and 4H-3,1-benzoxazines[J].J.Org.Chem.,2012,77(2):1 136-1 142.
[14]罗维,徐运启,苑丽红,等.2-(2-吡啶)-5,6,7,8-四氢吡啶并[4,3-d]嘧啶及其衍生物的合成[J].化学试剂,2017,39(2):191-194.
[15]黄志斌,刘学成,胡明华,等.吡啶并[2,3-d]嘧啶衍生物受体的合成及对阴离子识别研究[J].有机化学,2014,34(2):382-386.
[16]RIADI Y,GEESI M.Photochemical route for the synthesis of novel 2-mono substituted pyrido[2,3-d]pyrimidines by palladium-catalyzed cross-coupling reactions[J].Chem.Pap.,2018,72(3):697-701.