6-卤代咪唑并[1,2-a]吡啶-3-甲腈的一锅两步合成
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摘要
以2-氨基-5-卤代吡啶为原料,与N,N-二甲基甲酰胺二甲基缩醛(DMF-DMA)在DMF中反应,几乎定量得到(E)-N'-(5-卤代吡啶-2-基)-N,N-二甲基甲脒中间体。然后以KI为催化剂,在Na HCO3作用下,于"一锅中"甲脒中间体和溴乙腈发生反应得到标题化合物,总收率为59.2%~73.6%。产物结构通过IR、1HNMR、元素分析和MS进行了表征。
6-Haloimidazo[1,2-a]pyridines-3-carbonitriles were prepared from 2-amino-5-halopyridine via a two-step one-pot process,with the total yield of 59. 2% ~ 73. 6%. Firstly,2-amino-5-halopyridine reacted with N,N-dimethylformamide dimethyl acetyl( DMF-DMA) in DMF to afford( E)-N'-( 5-halopyridin-2-yl)-N,N-dimethylformamidines as intermediates almost quantitatively,and then followed by the reaction with bromoacetonitrile catalyzed by KI in one-pot furnishing the target compounds under the effect of Na HCO3. The structure were confirmed by IR,1HNMR,and MS techniques and elemental analysis.
6-Haloimidazo[1,2-a]pyridines-3-carbonitriles were prepared from 2-amino-5-halopyridine via a two-step one-pot process,with the total yield of 59. 2% ~ 73. 6%. Firstly,2-amino-5-halopyridine reacted with N,N-dimethylformamide dimethyl acetyl( DMF-DMA) in DMF to afford( E)-N'-( 5-halopyridin-2-yl)-N,N-dimethylformamidines as intermediates almost quantitatively,and then followed by the reaction with bromoacetonitrile catalyzed by KI in one-pot furnishing the target compounds under the effect of Na HCO3. The structure were confirmed by IR,1HNMR,and MS techniques and elemental analysis.
引文
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[2]XI Ning,PARK N.Heteroaromatic compounds as PI3 Kinase modulators and methods of use:US,0 134 133[P].2014-05-15.
[3]EASTWOOD P R,JACOB G R,JORDI B T,et al.Preparation of imidazopyridine derivatives as therapeutic JAK inhibitors:WO,2 011 076 419[P].2011-06-30.
[4]FISHER M H,LUSI A.Imidazo[1,2-a]pyridine anthelmintic and antifungal agents[J].J.Med.Chem.,1972,15(9):982-985.
[5]EASTWOOD P R,JACOB G R,ELENA G C,et al.Fused heteroaryl imidazolone derivatives as JAK inhibitors and their preparation and use for the treatment of diseases:EP,2 397 482[P].2011-12-21.
[6]KIM O,JEONG Y,LEE H,et al.Design and synthesis of imidazopyridine analogues as inhibitors of phosphoinositide 3-Kinase signaling and angiogenesis[J].J.Med.Chem.,2011,54(7):2 455-2 466.
[7]HUNTSMAN E,BALSELLS J.New method for the general synthesis of[1,2,4]triazolo[1,5-a]pyridines[J].J.Eur.J.Org.Chem.,2005,(17):3 761-3 765.
[8]杨倩,张雅峥,邵永久,等.碘化钾催化合成4-甲基邻苯二酚二乙酸二甲酯的工艺研究[J].高校化学工程学报,2014,28(1):78-83.