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Synthesis of N2-arylaminopyrimidine-5-carbonitrile derivatives via SNAr amination reaction

Shahnaz Rostamizadeh ,  Masoomeh Nojavan ,  Reza Aryan

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Citation:  Shahnaz Rostamizadeh, Masoomeh Nojavan, Reza Aryan. Synthesis of N2-arylaminopyrimidine-5-carbonitrile derivatives via SNAr amination reaction[J]. Chinese Chemical Letters, 2015, 26(1): 152-156. doi: 10.1016/j.cclet.2014.10.007 shu

Synthesis of N2-arylaminopyrimidine-5-carbonitrile derivatives via SNAr amination reaction

    • 通讯作者: Shahnaz Rostamizadeh,
摘要: An efficient and high-yielding synthesis of N2-arylaminopyrimidine-5-carbonitrile derivatives starting from arylamines and 2-methylthio-pyrimidine-5-carbonitrile derivatives has been developed in the presence of cesium carbonate as basic reagent. This new protocol showed high chemical tolerance for a range of functional groups, and only the methylthio substituent on C2 of the pyrimidine ring was replaced with arylamine derivatives under the reaction conditions.

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    1. [1] R. Capdeville, E. Buchdunger, J. Zimmermann, et al., Glivec (STI571, imatinib), a rationally developed, targeted anticancer drug, Nat. Rev. Drug Discov. 1 (2002) 493-502.[1] R. Capdeville, E. Buchdunger, J. Zimmermann, et al., Glivec (STI571, imatinib), a rationally developed, targeted anticancer drug, Nat. Rev. Drug Discov. 1 (2002) 493-502.

    2. [2] Z. Lin, F. Junhua, C. Jer-Hong, et al., Design, synthesis, and biological evaluation of pyrazolopyrimidine-sulfonamides as potent multiple-mitotic kinase (MMK) inhibitors (Part I), Bioorg. Med. Chem. Lett. 21 (2011) 5633-5637.[2] Z. Lin, F. Junhua, C. Jer-Hong, et al., Design, synthesis, and biological evaluation of pyrazolopyrimidine-sulfonamides as potent multiple-mitotic kinase (MMK) inhibitors (Part I), Bioorg. Med. Chem. Lett. 21 (2011) 5633-5637.

    3. [3] L.A. McDermott, M. Simcox, B. Higgins, et al., RO4383596, an orally active KDR, FGFR, and PDGFR inhibitor: synthesis and biological evaluation, Bioorg. Med. Chem. 13 (2005) 4835-4841.[3] L.A. McDermott, M. Simcox, B. Higgins, et al., RO4383596, an orally active KDR, FGFR, and PDGFR inhibitor: synthesis and biological evaluation, Bioorg. Med. Chem. 13 (2005) 4835-4841.

    4. [4] M. Sabat, J.C. VanRens, T.A. Brugel, et al., The development of novel 1,2-dihydropyrimido[ 4,5-c]pyridazine based inhibitors of lymphocyte specific kinase (Lck), Bioorg. Med. Chem. Lett. 16 (2006) 4257-4261.[4] M. Sabat, J.C. VanRens, T.A. Brugel, et al., The development of novel 1,2-dihydropyrimido[ 4,5-c]pyridazine based inhibitors of lymphocyte specific kinase (Lck), Bioorg. Med. Chem. Lett. 16 (2006) 4257-4261.

    5. [5] U.J. Heye, J. Speich, H. Siegle, et al., CGA 219417: a novel broad-spectrum fungicide, Crop Prot. 13 (1994) 541-549.[5] U.J. Heye, J. Speich, H. Siegle, et al., CGA 219417: a novel broad-spectrum fungicide, Crop Prot. 13 (1994) 541-549.

    6. [6] L.B. Johnson, L.D. Saravolatz, Etravirine, a next-generation nonnucleoside reversetranscriptase inhibitor, Clin. Infect. Dis. 48 (2009) 1123-1128.[6] L.B. Johnson, L.D. Saravolatz, Etravirine, a next-generation nonnucleoside reversetranscriptase inhibitor, Clin. Infect. Dis. 48 (2009) 1123-1128.

    7. [7] X.Q. Feng, Y.H. Liang, Z.S. Zeng, et al., Structural modifications of DAPY analogues with potent anti-HIV-1 activity, Chem. Med. Chem. 4 (2009) 219-224.[7] X.Q. Feng, Y.H. Liang, Z.S. Zeng, et al., Structural modifications of DAPY analogues with potent anti-HIV-1 activity, Chem. Med. Chem. 4 (2009) 219-224.

    8. [8] J.F. Hartwig, Approaches to catalyst discovery. New carbon-heteroatom and carbon-carbon bond formation, Pure Appl. Chem. 71 (1999) 1417-1423.[8] J.F. Hartwig, Approaches to catalyst discovery. New carbon-heteroatom and carbon-carbon bond formation, Pure Appl. Chem. 71 (1999) 1417-1423.

    9. [9] A.R. Muci, S.L. Buchwald, Practical palladium catalysts for C-N and C-O bond formation, Top. Curr. Chem. 219 (2002) 131-209.[9] A.R. Muci, S.L. Buchwald, Practical palladium catalysts for C-N and C-O bond formation, Top. Curr. Chem. 219 (2002) 131-209.

    10. [10] J.F. Hartwig, Carbon-heteroatom bond-forming reductive eliminations of amines, ethers, and sulfides, Acc. Chem. Res. 31 (1998) 852-860.[10] J.F. Hartwig, Carbon-heteroatom bond-forming reductive eliminations of amines, ethers, and sulfides, Acc. Chem. Res. 31 (1998) 852-860.

    11. [11] J.F. Hartwig, Transition metal catalyzed synthesis of arylamines and aryl ethers from aryl halides and triflates: scope and mechanism, Angew. Chem. Int. Ed. 37 (1998) 2046-2067.[11] J.F. Hartwig, Transition metal catalyzed synthesis of arylamines and aryl ethers from aryl halides and triflates: scope and mechanism, Angew. Chem. Int. Ed. 37 (1998) 2046-2067.

    12. [12] D.S. Surry, S.L. Buchwald, Biaryl phosphane ligands in palladium-catalyzed amination, Angew. Chem. Int. Ed. 47 (2008) 6338-6361.[12] D.S. Surry, S.L. Buchwald, Biaryl phosphane ligands in palladium-catalyzed amination, Angew. Chem. Int. Ed. 47 (2008) 6338-6361.

    13. [13] S.N. VanderWel, P.J. Harvey, D.J. McNamara, et al., Pyrido[2,3-d]pyrimidin-7-ones as specific inhibitors of cyclin-dependent kinase 4, J. Med. Chem. 48 (2005) 2371- 2387.[13] S.N. VanderWel, P.J. Harvey, D.J. McNamara, et al., Pyrido[2,3-d]pyrimidin-7-ones as specific inhibitors of cyclin-dependent kinase 4, J. Med. Chem. 48 (2005) 2371- 2387.

    14. [14] K.L. Sayle, J. Bentley, F.T. Boyle, et al., Structure-based design of 2-arylamino-4- cyclohexylmethyl-5-nitroso-6-aminopyrimidine inhibitors of cyclin-dependent kinases 1 and 2, Bioorg. Med. Chem. Lett. 13 (2003) 3079-3082.[14] K.L. Sayle, J. Bentley, F.T. Boyle, et al., Structure-based design of 2-arylamino-4- cyclohexylmethyl-5-nitroso-6-aminopyrimidine inhibitors of cyclin-dependent kinases 1 and 2, Bioorg. Med. Chem. Lett. 13 (2003) 3079-3082.

    15. [15] M.L. Maddess, R. Carter, SNAr reactions of 2-methylthio-4-pyrimidinones in pivalic acid: access to functionalized pyrimidinones and pyrimidines, Synthesis 44 (2012) 1109-1118.[15] M.L. Maddess, R. Carter, SNAr reactions of 2-methylthio-4-pyrimidinones in pivalic acid: access to functionalized pyrimidinones and pyrimidines, Synthesis 44 (2012) 1109-1118.

    16. [16] J. Spychala, A facile preparation N2-arylisocytosines, Synth. Commun. 27 (1997) 1943-1949.[16] J. Spychala, A facile preparation N2-arylisocytosines, Synth. Commun. 27 (1997) 1943-1949.

    17. [17] M. Barvian, D.H. Boschelli, J. Cossrow, et al., Pyrido[2,3-d]pyrimidin-7-one inhibitors of cyclin-dependent kinases, J. Med. Chem. 43 (2000) 4606-4616.[17] M. Barvian, D.H. Boschelli, J. Cossrow, et al., Pyrido[2,3-d]pyrimidin-7-one inhibitors of cyclin-dependent kinases, J. Med. Chem. 43 (2000) 4606-4616.

    18. [18] J. Spychala, K. Golankiewicz, The efficient method of synthesis of 4-N-arylcytosines, Synth. Commun. 20 (1990) 1899-1904.[18] J. Spychala, K. Golankiewicz, The efficient method of synthesis of 4-N-arylcytosines, Synth. Commun. 20 (1990) 1899-1904.

    19. [19] B. Sreedhar, P.S. Reddy, M.A. Reddy, Catalyst-free and base-free waterpromoted SNAr reaction of heteroaryl halides with thiols, Synthesis 10 (2009) 1732-1738.[19] B. Sreedhar, P.S. Reddy, M.A. Reddy, Catalyst-free and base-free waterpromoted SNAr reaction of heteroaryl halides with thiols, Synthesis 10 (2009) 1732-1738.

    20. [20] R.A. Altman, S.L. Buchwald, Cu-catalyzed Goldberg and Ullmann reactions of aryl halides using chelating N- and O-based ligands, Nat. Protoc. 2 (2007) 2474- 2479.[20] R.A. Altman, S.L. Buchwald, Cu-catalyzed Goldberg and Ullmann reactions of aryl halides using chelating N- and O-based ligands, Nat. Protoc. 2 (2007) 2474- 2479.

    21. [21] Y. Liu, Y. Bai, J. Zhang, et al., Optimization of the conditions for coppermediated N-arylation of heteroarylamines, Eur. J. Org. Chem. (2007) 6084- 6088.[21] Y. Liu, Y. Bai, J. Zhang, et al., Optimization of the conditions for coppermediated N-arylation of heteroarylamines, Eur. J. Org. Chem. (2007) 6084- 6088.

    22. [22] J.H.M. Lange, L.J.F. Hofmeyer, F.A.S. Hout, et al., Microwave-enhanced Goldberg reaction: a novel route to N-arylpiperazinones and N-arylpiperazinediones, Tetrahedron Lett. 43 (2002) 1101-1104.[22] J.H.M. Lange, L.J.F. Hofmeyer, F.A.S. Hout, et al., Microwave-enhanced Goldberg reaction: a novel route to N-arylpiperazinones and N-arylpiperazinediones, Tetrahedron Lett. 43 (2002) 1101-1104.

    23. [23] J. Ahmadi, S. Sadjadi, M. Hosseinpour, Granulated copper oxide nano-catalyst: a novel and efficient catalyst for C-N cross-coupling of amines with iodobenzene, Monatsh. Chem. 142 (2011) 801-806.[23] J. Ahmadi, S. Sadjadi, M. Hosseinpour, Granulated copper oxide nano-catalyst: a novel and efficient catalyst for C-N cross-coupling of amines with iodobenzene, Monatsh. Chem. 142 (2011) 801-806.

    24. [24] L. Pellegatti, E. Vedrenne, J.M. Leger, et al., First efficient palladium-catalyzed aminations of pyrimidines, 1,2,4-triazines and tetrazines by original methyl sulfur release, Synlett 13 (2009) 2137-2142.[24] L. Pellegatti, E. Vedrenne, J.M. Leger, et al., First efficient palladium-catalyzed aminations of pyrimidines, 1,2,4-triazines and tetrazines by original methyl sulfur release, Synlett 13 (2009) 2137-2142.

    25. [25] Sh. Rostamizadeh, M. Nojavan, An environmentally benign multicomponent synthesis of some novel 2-methylthio pyrimidine derivatives using MCM-41- NH2 as nanoreactor and nanocatalyst, J. Heterocycl. Chem. 51 (2014) 418-422.[25] Sh. Rostamizadeh, M. Nojavan, An environmentally benign multicomponent synthesis of some novel 2-methylthio pyrimidine derivatives using MCM-41- NH2 as nanoreactor and nanocatalyst, J. Heterocycl. Chem. 51 (2014) 418-422.

    26. [26] C.F. Bernasconi, M.C. Muller, P. Schmid, Intermediates in nucleophilic aromatic substitution. 20. Rate-limiting proton transfer in the formation of Meisenheimer complexes between 1,3,5-trinitrobenzene and amines. The effect of dimethyl sulfoxide on proton-transfer rates. Relative leaving-group abilities of amines and alkoxide ions, J. Org. Chem. 44 (1979) 3189-3196.[26] C.F. Bernasconi, M.C. Muller, P. Schmid, Intermediates in nucleophilic aromatic substitution. 20. Rate-limiting proton transfer in the formation of Meisenheimer complexes between 1,3,5-trinitrobenzene and amines. The effect of dimethyl sulfoxide on proton-transfer rates. Relative leaving-group abilities of amines and alkoxide ions, J. Org. Chem. 44 (1979) 3189-3196.

    27. [27] I. Gallardo, G. Guirado, J. Marquet, Nucleophilic aromatic substitution for heteroatoms: an oxidative electrochemical approach, J. Org. Chem. 67 (2002) 2548-2555.[27] I. Gallardo, G. Guirado, J. Marquet, Nucleophilic aromatic substitution for heteroatoms: an oxidative electrochemical approach, J. Org. Chem. 67 (2002) 2548-2555.

    28. [28] T. Flessner, S. Doye, Cesium carbonate: a powerful inorganic base in organic synthesis, J. Prakt. Chem. 341 (1999) 186-190.[28] T. Flessner, S. Doye, Cesium carbonate: a powerful inorganic base in organic synthesis, J. Prakt. Chem. 341 (1999) 186-190.

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  • 发布日期:  2014-10-13
  • 收稿日期:  2014-04-24
  • 网络出版日期:  2014-07-31
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