An Efficient Synthesis of Pyrido[2,3-d]pyrimidine Derivatives via One-Pot Three-Component Reaction in Aqueous Media

Abstract

A series of pyrido[2,3-d]pyrimidines derivatives have been prepared by one-pot three-component reaction of 4(6)-aminouracil, malononitrile and aromatic aldehydes. This efficient synthesis was done under microwave irradiation conditions (method A) and also using catalytic amount of diammonium hydrogen phosphate [(NH4)2HPO4] (DAHP) in aqueous media (method B). This procedure has the advantages of good yields, easy work-up, and benign environmentally friendly character. Reaction could proceed via domino Knoevenagel-Michael-cyclization reactions.

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S. Abdolmohammadi and S. Balalaie, "An Efficient Synthesis of Pyrido[2,3-d]pyrimidine Derivatives via One-Pot Three-Component Reaction in Aqueous Media," International Journal of Organic Chemistry, Vol. 2 No. 1, 2012, pp. 7-14. doi: 10.4236/ijoc.2012.21002.

Conflicts of Interest

The authors declare no conflicts of interest.

References

[1] L. V. G. Nargund, Y. S. R. Reddy and R. Jose, “Synthesis and Antibacterial Activity of Pyrido[1, 2-a]pyrimidin-4 (1H)—Ones,” Indian Drugs, Vol. 29, No. 1, 1991, pp. 45-46.
[2] A. D. Broom, J. L. Shim and G. L. Anderson, “Pyrido[2,3-d]pyrimidines. IV. Synthetic Studies Leading to Various Oxopyrido[2,3-d]pyrimidines,” Journal of Organic Chemistry, Vol. 41, No. 7, 1976, pp. 1095-1099. doi:10.1021/jo00869a003
[3] E. M. Grivsky, S. Lee, C. W. Sigel, D. S. Duch and C. A. Nichol, “Synthesis and Antitumor Activity of 2,4-Diamino-6-(2,5-dimethoxybenzyl)-5-methylpyrido[2,3-d]pyrimidine,” Journal of Medicinal Chemistry, Vol. 23, 1980, pp. 327-329. doi:10.1021/jm00177a025
[4] K. Furukawa and T. Hasegawa, “Preparation of Pyrido[2, 3-d]pyrimidine-2,4-di-one Derivatives as Antiasthmatics and Antiallergics,” Chemical Abstracts, Vol. 124, 1996, 289568c.
[5] A. Rosowsky, C. E. Mota, S. F. Queener, “Synthesis and Antifolate Activity of 2,4-Diamino-5,6,7,8-tetrahydro- pyrido[4,3-d]pyrimidine Ana-logues of Trimetrexate and Piritrexim,” Journal of Heterocyclic Chemistry, Vol. 32, No. 1, 1995, pp. 335-340. doi:10.1002/jhet.5570320155
[6] A. M. Thompson, A. J. Bridges, D. W. Fry, A. J. Kraker and W. A. Denny, “Tyrosine Kinase Inhibitors.7.7-ami- no-4-(phenylamino)-and7-amino-4-[(phenylmethyl)amino] pyrido [4,3-d]pyrimidines: A New Class of Inhibitors of the Tyrosine Kinase Activity of the Epidermal Growth Factor Receptor,” Journal of Medicinal Chemistry, Vol. 38, 1995, pp. 3780-3788. doi:10.1021/jm00019a007
[7] I.O. Donkor, C. L. Klein, L. Liang, N. Zhu, E. Bradley, and A. M. Clark, “Synthesis and Antimicrobial Activity of Some 6,7-Annulated Pyri-do[2,3-d]pyrimidines,” Journal of Pharmaceutical Sciences, Vol. 84, No. 5, 1995, pp. 661- 664. doi:10.1002/jps.2600840526
[8] A. Pastor, R. Alajarin, J. J. Vaquero, J. Alvarez-Builla, M. F. d. Casa-Juana, C. Sunkel, J. G. Priego, I. Fonseca and J. Sanz-Aparicio, “Synthesis and Structure of New Pyrido[2,3-d]pyrimidine Derivatives with Calcium Channel Antagonist Activity,” Tetrahedron, Vol. 50, No. 27, 1994, pp. 8085-8098. doi:10.1016/S0040-4020(01)85291-1
[9] J. Matsumoto and S. Minami, “Pyrido[2,3-d]pyrimidine Antibacterial Agents. 3. 8-Alkyl- and 8-vinyl-5,8-dihy- dro-5-oxo-2-(1-piperazinyl)pyrido[2,3-d]pyrimidine-6-carboxylic Acids and Their Derivatives,” Journal of Medicinal Chemistry, Vol. 18, 1975, pp. 74-79. doi:10.1021/jm00235a017
[10] N. Suzuki, “Synthesis of Antimicrobial Agents. V. Synthesis and Antimicrobial Activities of Some Heterocyclic Condensed 1, 8-Naphthyridine Derivatives,” Chemical & Pharmaceutical Bulletin, Vol. 28, No. 3, 1980, pp. 761- 768. doi:10.1248/cpb.28.761
[11] V. Oakes and H. N. Rydon, “Polyazanaphthalenes. Part IV. Further derivatives of 1:3:5- and 1:3:8-triazanaphthalene,” Journal of the Chemical Society, 1956, pp. 4433-4438. doi:10.1039/jr9560004433
[12] J. I. Degraw, R. L. Kisliuk, Y. Gaumont and C. M. Baugh, “Antimicrobial Activity of 8-Deazafolic Acid,” Journal of Medicinal Chemistry, Vol. 17, No. 4, 1974, pp. 470- 471. doi:10.1021/jm00250a026
[13] V. E. Kolla, A. B. Deyanov, F. Y. Nazmetdinov, Z. N. Kashina and L. P. Drovosekova, “Investigation of the Anti-Inflammatory and Analgesic Activity of 2-Substi- tuted 1-Aryl-6-carboxy-(carbethoxy)-7-methyl-4-oxo-1,4- dihydropy-rido[2,3-d]pyrimidines,” Journal of Pharmaceutical Chemistry, Vol. 27, No. 9, 1993.
[14] J. W. Ellingboe and N. J. Princeton, “Substituted Pyridopyrimidines and Antihypertensives,” Chemical Abstracts, Vol. 124, 1996, Article ID: 176134q.
[15] A. Agarwal, R. Ashutosh, N. Goyal, P. M. S. Chauhan and S. Gupta, “ Dihydropyrido [2,3-d]pyrimidines as a New Class of Antileishmanial Agents,” Journal of Bioorganic & Medicinal Chemistry, Vol. 13, No. 24, 2005, pp. 6678-6684.
[16] I. D. Bystryakova, O. A. Burova, G. M. Che-lysheva, S. V. Zhilinkova, N. M. Smirnova and T. S. Safonova, “Synthesis and Biological Activity of Pyridol[2,3-d]py- rimi-dines,” Journal of Pharmaceutical Chemistry, Vol. 25, No. 12, 1991, pp. 874-876. doi:10.1007/BF00778976
[17] A. B. Deyanov, R. K. Niyazov, F. Y. Nazmetdivov, B. Y. Syropyatov, V. E. Kolla and M. E. Konshin. “Synthesis and Biological Activity of Amides and Nitriles of 2- Arylami-no-5-carboxy(carbethoxy)-6-methylnicotinic acids and 1-aryl-6-carbethoxy-7-methyl-4-oxo-1,4-dihydro- pyri-do[2,3-d]pyrimidines,” Journal of Pharmaceutical Chemistry, Vol. 25, No. 4, 1991, pp. 248-250. doi:10.1007/BF00772106
[18] A. Monge, V. Martinez-Merino, C. Sanmartin, F. J. Fernandez, M. C. Ochoa, C. Berllver, P. Artigas and E. Fernandez-Alvarez, “2-Arylamino-4-oxo-3,4-dihydropyrido-[2, 3-d]pyrimidines: Synthesis and Diuretic Activity,” European Journal of Medicinal Chemistry, Vol. 24, No. 3, 1989, pp. 24-209. doi:10.1016/0223-5234(89)90001-9
[19] H. Saladowska, A. Bartoszko-Malik and T. Zawisza, “Synthesis and Properties of New Derivatives of Ethyl 7-Methyl-2,4-dioxo-1,2,3,4-tetrahydropyrido [2,3- d]pyri- mi-dine-5-carboxylate,” Farmaco, Vol. 45, No. 1, 1990, pp. 101-110.
[20] P. A. Grieco, “Organic Synthesis in Water,” Blackie Academic & Professional, London, 1998.
[21] C.-J. Li and T. H. Chan, “Comprehensive Organic Reactions in Aqueous Media,” John Wiley &Sons, Inc., Hoboken, 2007.
[22] C.-J. Li. “Organic Reactions in Aqueous Media with a Focus on Carbon-Carbon Bond Formations: A Decade Update,” Chemical Reviews, Vol. 105, No. 8, 2005, pp. 3095-3166. doi:10.1021/cr030009u
[23] C.-J. Li, “Organic Reactions in Aqueous Media—With a Focus on Carbon-Carbon Bond Formation,” Chemical Reviews, Vol. 93, No. 6, 1993, pp. 2023-2035. doi:10.1021/cr00022a004
[24] U. M. Lindstr?m, “Stereoselective Organic Reactions in Water,” Chemical Reviews, Vol. 102, No. 8, 2002, pp. 2751-2772. doi:10.1021/cr010122p
[25] M. C. Pirrung, “Acceleration of Organic Reactions through Aqueous Solvent Effects,” Chemistry A European Journal, Vol. 12, No. 5, 2006, pp. 1312-1317. doi:10.1002/chem.200500959
[26] K. V. Katkar, P. S. Chaudhari and K. G.Akamanchi, “Sulfated Tungstate: An Efficient Catalyst for the Ritter Reaction,” Green Chemistry, Vol. 13, No. 4. 2011, pp. 835- 838. doi:10.1039/c0gc00759e
[27] J. Quiroga, M. Alvarado, B. Insuasty, M. Nogueras, A, Sanchez and J. Cobo, “Synthesis of 6-Cyanopy- ri-do[2,3-d]pyrimidinones in the Reaction of 6-Amino- 4-pyrimidinones with Arylidene Derivatives of Malonodinitrile,” Journal of Heterocyclic Chemistry, Vol. 35, No. 6, 1998, pp. 1309-1311. doi:10.1002/jhet.5570350612
[28] M. N. Nasr and M. M. Gineinah, “Pyrido[2,3-d]py- rimidines and Pyrimido[5′,4′:5, 6]pyrido [2,3-d]pyri-midines as New Antiviral Agents: Synthesis and Biological Activity,” Journal of Heterocyclic Compounds, Vol. 33, No. 50, 2002, pp. 118.
[29] X.-S. Wang, Z.-S. Zeng, D.-Q. Shi, X.-Y. Wei and Z.-M. Zong, “KF-Alumina Catalyzed One-Pot Synthesis of Pyrido[2,3-d]Pyrimidine Derivatives,” Synthetic Communi-cations, Vol. 34, No. 23, 2004, pp. 4331-4338. doi:10.1081/SCC-200039392
[30] X.-S. Wang, Z.-S Zeng, D.-Q. Shi, S.-J. Tu, X.-Y. Wei and Z.-M. Zong, “Three-Component, One-Pot Synthesis of Pyri-do[2,3-d]pyrimidine Derivatives Catalyzed by KF-Alumina,” Synthetic Communications, Vol. 35, No. 14, 2005, pp. 1921-1927. doi:10.1081/SCC-200064984
[31] S. Youssif and F. Z.Agili, “ChemInform Abstract: One-Pot Synthesis of Fused 2-Thiouracils: Pyrimido- pyrimidines, Pyridopyrimidines and Imidazolopyrimi- dines,” Journal of Preparative Organic Chem-istry, Vol. 39, No. 43, 2008.
[32] D. Shi, S. Ji, L. Niu, J. Shi and X. Wang, “One-Pot Synthesis of Pyrido[2,3-d]pyrimidines via Efficient Three-Component Reaction in Aqueous Media,” Journal of Heterocyclic Chemistry, Vol. 44, No. 5, 2007, pp. 1083-1090. doi:10.1002/jhet.5570440517
[33] D-Q. Shi, Y. Zhou and H. Liua, “An Efficient Synthesis of Pyrido[2,3-d]pyrimidine Derivatives in Ionic Liquid,” Journal of Heterocyclic Chemistry, Vol. 47, No. 1, 2010, pp. 131-135.
[34] A. Loupy, “Microwave in Organic Synthesis,” Wiley- VCH, Weinheim, 2002, pp. 147-180. doi:10.1002/3527601775.ch5
[35] R. S. Varma, “Solvent-Free Organic Syntheses. Using Supported Reagents and Microwave Irradiation,” Green Chemistry, Vol. 1, No. 1, 1999, pp. 43-55. doi:10.1039/a808223e
[36] C. O. Kappe, “Controlled Microwave Heating in Modern Organic Synthesis,” Angewandte Chemie International Edition, Vol. 43, No. 46, 2004, pp. 6250-6284. doi:10.1002/anie.200400655
[37] B. L. Hayes, “Recent Advances in Microwave-Assisted Synthesis,” Aldrichimica Acta, Vol. 37, No. 2, 2004, pp. 66-77.
[38] R. J. Lewis, “Hawley’s Condensed Chemical Dictionary,” 13th Edition, Von Nostrand Reinhold, New York, 1997.
[39] S.-J. Tu, B. Jiang, R.-H. Jia, J.-Y. Zhang, Y. Zhang, C.-S. Yao and F. Shi, “An Efficient One-Pot, Three-Component Synthesis of Indeno[1,2-b]quinoline-9,11(6H,10H)- dione, Acri-dine-1,8(2H,5H)-dione and Quinoline-3-car-bonitrile Derivatives from Enaminones,” Organic & Biomolecular Chemistry, Vol. 4, No. 16, 2006, pp. 3664- 3668. doi:10.1039/b607575d
[40] S.-J. Tu, B. Jiang, J.-Y. Zhang, R.-H. Jia, Y. Zhang and C.-S. Yao, “Efficient and Direct Synthesis of Poly-Substituted Indeno[1,2-b]quinolines Assisted by P-Toluene Sulfonic Acid Using High-Temperature Water and Microwave Heating via One-Pot, Three-Component Reaction,” Organic & Biomolecular Chemistry, Vol. 4, No. 21, 2006, pp. 3980-3985. doi:10.1039/b611462h
[41] S. Balalaie, M. Bararjanian, S. Hekmat and P. Salehi, “Novel, Efficient, and Green Procedure for the Knoevenagel Condensation Catalyzed by Diammonium Hydrogen Phosphate in Water,” Synthetic Communications, Vol. 36, No.17, 2006, pp. 2549-2557. doi:10.1080/00397910600781471
[42] F. Darvich, S. Balalaie, F. Chadegani and P. Salehi, “Diammonium Hydrogen Phosphate as a Neutral and Efficient Catalyst for Synthesis of 1,8-Dioxo-octahy- droxanthene Derivatives in Aqueous Media,” Synthetic Communications, Vol. 37. No. 7, 2007, pp. 1059-1066. doi:10.1080/00397910701196520
[43] S. Balalaie, M. Bararjanian, S. Hekmat, M. Sheikh- Ahmadi and P. Salehi, “Diammonium Hydrogen Phosphate: An Efficient and Versatile Catalyst for the One-Pot Synthesis of Tetrahydrobenzo[b]pyran Derivatives in Aqueous Media,” Synthetic Communications, Vol. 37, No. 7, 2007, pp. 1097-1108. doi:10.1080/00397910701196579
[44] S. Abdolmohammadi and S. Balalaie, “Novel and Efficient Catalysts for the One-Pot Synthesis of 3,4-Dihy- dropyrano[c]chromene Derivatives in Aqueous Media,” Tetrahedron Letters, Vol. 48, No. 18, 2007, pp. 3299- 3303. doi:10.1016/j.tetlet.2007.02.135
[45] S. Balalaie, S. Abdolmohammadi, H. R. Bijanzadeh and A. M. Amani, “Diammonium Hydrogen Phosphate as a Versatile and Efficient Catalyst for the One-Pot Synthesis of Pyra-no[2,3-d]pyrimidinone Derivatives in Aqueous Media,” Mole-cular Diversity, Vol 12, No. 2, 2008, pp. 85-91. doi:10.1007/s11030-008-9079-7

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