铜催化酰胺和溴代嘧啶胺的碳氮偶联反应
|
摘要
用CuI作催化剂,对N-(5-溴-2-甲苯基)-4-(3-吡啶基)-2-嘧啶胺和一些系列酰胺的C-N偶联反应进行了研究。通过条件试验,对适配碱的种类、溶剂、配体以及用量进行了筛选。并选用D-抗坏血酸钠作为抗氧剂,使偶联反应在开放的体系中方便地进行。方法简便,产率较高。采用该方法合成出了靶向抗癌药伊马替尼(格列卫),以及一些具有相似结构的N-嘧啶胺基苯基取代苯甲酰胺类衍生物。
The C-N coupling reaction of N-(5-bromo-2-methylphenyl)-4-(pyridin-3-yl) pyrimidin-2-amine with a series of amides was studied using CuI as catalyst. The types and dosage of adapted alkali,solvents and ligands were screened through conditional tests. D-sodium ascorbate was chosen as antioxidant to facilitate the coupling reaction in an open system. The method is simple and the yield is high. The synthesis of the targeted anticancer drug imatinib( Gleevec),and some N-pyrimidine aminophenyl substituted benzamides derivatives was accomplished by this method.
The C-N coupling reaction of N-(5-bromo-2-methylphenyl)-4-(pyridin-3-yl) pyrimidin-2-amine with a series of amides was studied using CuI as catalyst. The types and dosage of adapted alkali,solvents and ligands were screened through conditional tests. D-sodium ascorbate was chosen as antioxidant to facilitate the coupling reaction in an open system. The method is simple and the yield is high. The synthesis of the targeted anticancer drug imatinib( Gleevec),and some N-pyrimidine aminophenyl substituted benzamides derivatives was accomplished by this method.
引文
[1]TIELEN R VERHOEF C VAN COEVORDEN F,et al.Surgical treatment of locally advanced,non-metastatic,gastrointestinal stromaltumours after treatment with imatinib[J].European Journal of Surgical Oncology,2013,39:15015.
[2]STEGMEIER F WARMUTH M SELLERS W R,et al.Targeted cancer therapies in the twenty-first century:Lessons from imatinib[J].Clin Pharmacol Ther,2010,87(5):54352.
[3]MORREN M-A HOPP A RENARD M,et al.Imatinib mesylate in the treatment of diffuse cutaneous Mastocytosis[J].Clinical and Laboratory Observations,2013,162(1):205-207.
[4]PAUL F,PATT J,HARTWIG J F.Palladium-catalyzed formation of carbon-nitrogen bonds.Reaction intermediates and catalyst improvements in the hetero cross-coupling of aryl halides and tin amides[J].Journal of the American Chemical Society,1994,116(13):5969-5970.
[5]MA F,XIE X,ZHANG L,et al.Palladium-catalyzed amidation of aryl halides using 2-dialkylphosphino-2'-alkoxyl-1,1'-binaphthyl as Ligands[J].J Org Chem,2012,77:52795285.
[6]WOLFE J P,RENNELS R A,BUCHWALD S L.Intramolecular palladium-catalyzed aryl amination and aryl amidation[J].Tetrahedron,1996,52(21):7525-7546.
[7]MA D,ZHANG Y,YAO J,et al.Accelerating effect induced by the structure ofα-amino acid in the copper-catalyzed coupling reaction of aryl halides withα-amino acids.Synthesis of benzolactam-V8[J].Journal of the American Chemical Society,1998,120(48):12459-12467.
[8]KLAPARS A,HUANG X,BUCHWALD S L.A general and efficient copper catalyst for the amidation of aryl halides[J].Journal of the American Chemical Society,2002,124(25):7421-7428.
[9]XU H,WOLF C.Copper catalyzed coupling of aryl chlorides,bromides and iodideswith amines and amides[J].Chem Commun,2009,(13):1715-1717.
[10]QUAN Z J,XIA H D,ZHANG Z,et al.An efficient copper-catalyzed N-arylation of amides:Synthesis of N-arylacrylamides and 4-amido-N-phenylbenzamides[J].Tetrahedron,2013,69:8368-8374.
[11]TEO Y C,YONG F F,ITHNIN I K,et al.Efficient manganese/copper bimetallic catalyst for N-arylation of amides and sulfonamides under mild conditions in water[J].Eur J Org Chem,2013,(3):515-524.
[12]YAO Z,WEI X.Amidation of aryl halides catalyzed by the efficient and recyclable Cu2O nanoparticles[J].Chin J Chem,2010,28:2260-2268.
[13]HOSSEINZADEH R,TAJBAKHSH M,MOHADJERA-NI M,et al.Cu I-catalyzed coupling reactions of aryl iodides with amides using L-Proline and KF/Al2O3[J].Chinese Journal of Chemistry,2008,26(11):2120-2124.
[14]殷玉英,刘毅锋,张娟,等.以偏铝酸钠为催化剂实现由芳香甲腈到芳香甲酰胺的转化[J].化学试剂,2015,38(1):55-59.
[15]白亚军,刘毅锋,张娟,等.3-N,N-二甲氨基-1-芳杂环基-2-丙烯-1-酮合成的研究[J].西北大学学报(自然科学版),2007,37(2):231-234.
[16]GRAMMATICAKIS P.Remarks about the preparation and ultraviolet absorption of some o-,m-,and pmethylbenzoylarylamines[J].Compt Rend,1962,255:1456-1458.
[17]LIU Y F,WANG C L,BAI Y J,et al.A facile total synthesis of imatinib base and its analogues[J].Organic Process Research&Development,2008,12(3):490-495.
[2]STEGMEIER F WARMUTH M SELLERS W R,et al.Targeted cancer therapies in the twenty-first century:Lessons from imatinib[J].Clin Pharmacol Ther,2010,87(5):54352.
[3]MORREN M-A HOPP A RENARD M,et al.Imatinib mesylate in the treatment of diffuse cutaneous Mastocytosis[J].Clinical and Laboratory Observations,2013,162(1):205-207.
[4]PAUL F,PATT J,HARTWIG J F.Palladium-catalyzed formation of carbon-nitrogen bonds.Reaction intermediates and catalyst improvements in the hetero cross-coupling of aryl halides and tin amides[J].Journal of the American Chemical Society,1994,116(13):5969-5970.
[5]MA F,XIE X,ZHANG L,et al.Palladium-catalyzed amidation of aryl halides using 2-dialkylphosphino-2'-alkoxyl-1,1'-binaphthyl as Ligands[J].J Org Chem,2012,77:52795285.
[6]WOLFE J P,RENNELS R A,BUCHWALD S L.Intramolecular palladium-catalyzed aryl amination and aryl amidation[J].Tetrahedron,1996,52(21):7525-7546.
[7]MA D,ZHANG Y,YAO J,et al.Accelerating effect induced by the structure ofα-amino acid in the copper-catalyzed coupling reaction of aryl halides withα-amino acids.Synthesis of benzolactam-V8[J].Journal of the American Chemical Society,1998,120(48):12459-12467.
[8]KLAPARS A,HUANG X,BUCHWALD S L.A general and efficient copper catalyst for the amidation of aryl halides[J].Journal of the American Chemical Society,2002,124(25):7421-7428.
[9]XU H,WOLF C.Copper catalyzed coupling of aryl chlorides,bromides and iodideswith amines and amides[J].Chem Commun,2009,(13):1715-1717.
[10]QUAN Z J,XIA H D,ZHANG Z,et al.An efficient copper-catalyzed N-arylation of amides:Synthesis of N-arylacrylamides and 4-amido-N-phenylbenzamides[J].Tetrahedron,2013,69:8368-8374.
[11]TEO Y C,YONG F F,ITHNIN I K,et al.Efficient manganese/copper bimetallic catalyst for N-arylation of amides and sulfonamides under mild conditions in water[J].Eur J Org Chem,2013,(3):515-524.
[12]YAO Z,WEI X.Amidation of aryl halides catalyzed by the efficient and recyclable Cu2O nanoparticles[J].Chin J Chem,2010,28:2260-2268.
[13]HOSSEINZADEH R,TAJBAKHSH M,MOHADJERA-NI M,et al.Cu I-catalyzed coupling reactions of aryl iodides with amides using L-Proline and KF/Al2O3[J].Chinese Journal of Chemistry,2008,26(11):2120-2124.
[14]殷玉英,刘毅锋,张娟,等.以偏铝酸钠为催化剂实现由芳香甲腈到芳香甲酰胺的转化[J].化学试剂,2015,38(1):55-59.
[15]白亚军,刘毅锋,张娟,等.3-N,N-二甲氨基-1-芳杂环基-2-丙烯-1-酮合成的研究[J].西北大学学报(自然科学版),2007,37(2):231-234.
[16]GRAMMATICAKIS P.Remarks about the preparation and ultraviolet absorption of some o-,m-,and pmethylbenzoylarylamines[J].Compt Rend,1962,255:1456-1458.
[17]LIU Y F,WANG C L,BAI Y J,et al.A facile total synthesis of imatinib base and its analogues[J].Organic Process Research&Development,2008,12(3):490-495.