In this report, synthesis of indenopyrido[2,3-d]pyrimidine and pyrimido[4,5-b]quinoline derivatives was investigated via one-pot three-component reaction between 6-amino-2-(alkylthio)-pyrimidin-4(3H)one, 1,3-indanedione, or 1,3-cyclohexadione and arylaldehyde under ultrasonic irradiation in ethylene glycol as solvent at 65°C. In these reactions fused pyrimidine derivatives were synthesized with high to excellent yields (82–97%) and short reaction times (10–33？min). 1. Introduction Pyrimidine structural moiety constitutes a major class of heterocyclic compounds which have various pharmaceutical applications. For example, they are found to possess antineoplastic [1–3], antiviral [4–6], antibiotic [7], and anti-inflammatory properties [8]. Pyrimidines also exhibit a range of pharmacological activities such as antibacterial [9–11], antifungal [12, 13], anticancer [14, 15], and cardioprotective effects [16]. Bicyclic and tricyclic fused pyrimidine derivatives have received much attention in connection with biologically significant systems such as pyrido[2,3-d]pyrimidines. Pyrido[2,3-d]pyrimidine structural motif is present in pirenperone (tranquilizer) [17] and ramastine (antiallergic) [18], as well as in some antiulcerative and antiasthmatic agents [19]. In addition, quinolines have pharmacological properties which include wide applications in medicinal chemistry; for example, this scaffold structure is present in anti-inflammatory agents, antimalarial drugs, and antihypertensive, antiasthmatic, antibacterial, and tyrosine kinase inhibiting agents [20–25]. Moreover the importance of uracil and its annulated derivatives is well recognized by synthetic [26, 27] as well as biological [28, 29] chemists. The 6-amino-uracil derivatives represent very important classes of functionalized uracils; also 6-amino-uracils find wide applications as starting materials for the synthesis of a number of fused uracils of biological significance, for example, pyrano-, pyrido-, pyrazolo-, pyrimido-, and pyridazinopyrimidines [30, 31]. On the other hand, ultrasonic reactions have been increasingly used as clean, green, and environmentally benign routes for the preparation of organic compounds of synthetic and biological values [32–37]. A large number of organic reactions can be carried out in higher yield, shorter reaction time, and under milder conditions, by using ultrasonic irradiation [38–41]. These observations led us to attempt the synthesis of some new fused pyrimidine derivatives using 6-amino-alkyltiouracil as starting material under sonochemical conditions. The present
References
[1]
S. A. Giller, R. A. Zhuk, and M. I. U. Lidak, “Analogs of pyrimidine nucleosides. I. N1-(alpha-furanidyl) derivatives of natural pyrimidine bases and their antimetabolities,” Doklady Akademii nauk SSSR, vol. 176, no. 2, pp. 332–335, 1967.
[2]
A. R. Curreri, F. J. Ansfield, F. A. McIver, H. A. Waisman, and C. Hedelberger, “Clinical studies with 5-fluorouracil,” Cancer Research, vol. 18, no. 4, pp. 478–484, 1958.
[3]
N. K. Chaudhary, B. J. Montag, and C. Heidelberger, “Studies on fluorinated pyrimidines: III. The metabolism of 5-fluorouracil-2-C14 and 5-fluoroorotic-2-C14 acid in vivo,” Cancer research, vol. 18, no. 3, pp. 318–328, 1958.
[4]
V. Malik, P. Singh, and S. Kumar, “Unique chlorine effect in regioselective one-pot synthesis of 1-alkyl-/allyl-3-(o-chlorobenzyl) uracils: anti-HIV activity of selected uracil derivatives,” Tetrahedron, vol. 62, no. 25, pp. 5944–5951, 2006.
[5]
A. Holy, I. Votruba, M. Masojídková et al., “6-[2-(Phosphonomethoxy)alkoxy] pyrimidines with antiviral activity,” Journal of Medicinal Chemistry, vol. 45, no. 9, pp. 1918–1929, 2002.
[6]
P. Andres and A. Marhold, “A new synthesis of 5-trifluoromethyluracil,” Journal of Fluorine Chemistry, vol. 77, no. 1, pp. 93–95, 1996.
[7]
J. J. Reddick, S. Saha, J.-M. Lee, J. S. Melnick, J. Perkins, and T. P. Begley, “The mechanism of action of bacimethrin, a naturally occurring thiamin antimetabolite,” Bioorganic and Medicinal Chemistry Letters, vol. 11, no. 17, pp. 2245–2248, 2001.
[8]
B. Gauthier, “On the thiamines with an open thiazole ring. study of O, S-diacetylthiamine,” Annales Pharmaceutiques Fran？aises, vol. 21, pp. 655–666, 1963.
[9]
E. Wyrzykiewicz, G. Bartkowiak, Z. Nowakowska, and B. Kedzia, “Synthesis and antimicrobial properties of S-substituted derivatives of 2-thiouracil,” Farmaco, vol. 48, no. 7, pp. 979–988, 1993.
[10]
P. Sharma, N. Rane, and V. K. Gurram, “Synthesis and QSAR studies of pyrimido[4,5-d]pyrimidine-2,5-dione derivatives as potential antimicrobial agents,” Bioorganic and Medicinal Chemistry Letters, vol. 14, no. 16, pp. 4185–4190, 2004.
[11]
Y. M. Elkholy and M. A. Morsy, “Facile synthesis of 5, 6, 7, 8-tetrahydropyrimido [4, 5-b]-quinoline derivatives,” Molecules, vol. 11, no. 11, pp. 890–903, 2006.
[12]
B. S. Holla, M. Mahalinga, M. S. Karthikeyan, P. M. Akberali, and N. S. Shetty, “Synthesis of some novel pyrazolo[3,4-d]pyrimidine derivatives as potential antimicrobial agents,” Bioorganic and Medicinal Chemistry, vol. 14, no. 6, pp. 2040–2047, 2006.
[13]
N. Ingarsal, G. Saravanan, P. Amutha, and S. Nagarajan, “Synthesis, in vitro antibacterial and antifungal evaluations of 2-amino-4-(1-naphthyl)-6-arylpyrimidines,” European Journal of Medicinal Chemistry, vol. 42, no. 4, pp. 517–520, 2007.
[14]
X. L. Zhao, Y. F. Zhao, S. C. Guo, H. S. Song, D. Wang, and P. Gong, “Synthesis and anti-tumor activities of novel [1,2,4]triazolo[1,5-a] pyrimidines,” Molecules, vol. 12, no. 5, pp. 1136–1146, 2007.
[15]
L. Cordeu, E. Cubedo, E. Bandrés et al., “Biological profile of new apoptotic agents based on 2,4-pyrido[2,3-d]pyrimidine derivatives,” Bioorganic and Medicinal Chemistry, vol. 15, no. 4, pp. 1659–1669, 2007.
[16]
N. M. Khalifa, N. S. Ismail, and M. M. Abdulla, “Synthesis and reactions of fused cyanopyrimidine derivatives and related glycosides as antianginal and cardio protective agents,” Egyptian Pharmaceutical Journal, vol. 4, pp. 277–288, 2005.
[17]
R. L. Smith, R. J. Barrett, and E. Sanders-Bush, “Neurochemical and behavioral evidence that quipazine-ketanserin discrimination is mediated by serotonin 2A receptor,” Journal of Pharmacology and Experimental Therapeutics, vol. 275, no. 2, pp. 1050–1057, 1995.
[18]
F. Awouters, J. Vermeire, F. Smeyers, et al., “Oral antiallergic activity in ascaris hypersensitive dogs: a study of known antihistamines and of the new compounds ramastine (R 57 959) and levocabastine (R 50 547),” Drug Development Research, vol. 8, no. 1–4, pp. 95–102, 1986.
[19]
Y. Yanagihara, H. Kasai, T. Kawashima, and T. Shida, “Immunopharmacological studies on TBX, a new antiallergic drug (1). Inhibitory effects on passsive cutaneous anaphylaxis in rats and guinea pigs,” The Japanese Journal of Pharmacology, vol. 48, no. 1, pp. 91–101, 1988.
[20]
R. D. Larsen, E. G. Corley, A. O. King et al., “Practical route to a new class of LTD4 receptor antagonists,” The Journal of Organic Chemistry, vol. 61, no. 10, pp. 3398–3405, 1996.
[21]
Y.-L. Chen, K.-C. Fang, J.-Y. Sheu, S.-L. Hsu, and C.-C. Tzeng, “Synthesis and antibacterial evaluation of certain quinolone derivatives,” Journal of Medicinal Chemistry, vol. 44, no. 14, pp. 2374–2377, 2001.
[22]
G. Roma, M. Di Braccio, G. Grossi, F. Mattioli, and M. Ghia, “1 ,8 -Naphthyridines IV. 9-Substituted N, N -dialkyl-5-(alkylamino or cycloalkylamino) [1,2,4] triazolo [4,3- a][1,8]naphthyridine-6-carboxamides, new compounds with anti-aggressive and potent anti-inflammatory activities,” European Journal of Medicinal Chemistry, vol. 35, no. 11, pp. 1021–1035, 2000.
[23]
D. Dubé, M. Blouin, C. Brideau, et al., “Quinolines as potent 5-lipoxygenase inhibitors: synthesis and biological profile of L-746,530,” Bioorganic & Medicinal Chemistry Letters, vol. 8, no. 10, pp. 1255–1260, 1998.
[24]
M. P. Maguire, K. R. Sheets, K. McVety, A. P. Spada, and A. Zilberstein, “A new series of PDGF receptor tyrosine kinase inhibitors: 3-Substituted quinoline derivatives,” Journal of Medicinal Chemistry, vol. 37, no. 14, pp. 2129–2137, 1994.
[25]
O. Billker, V. Lindo, M. Panico et al., “Identification of xanthurenic acid as the putative inducer of malaria development in the mosquito,” Nature, vol. 392, no. 6673, pp. 289–292, 1998.
[26]
T. K. Bradshaw and D. W. Hutchinson, “5-Substituted pyrimidine nucleosides and nucleotides,” Chemical Society Reviews, vol. 6, no. 1, pp. 43–62, 1977.
[27]
T. Sasaki, K. Minamoto, T. Suzuki, and S. Yamashita, “Search for a simpler synthetic model system for intramolecular 1,3-dipolar cycloaddition to the 5,6-double bond of a pyrimidine nucleoside,” Tetrahedron, vol. 36, no. 7, pp. 865–870, 1980.
[28]
R. Marumoto and Y. Furukawa, “Kondensierte pyrimidine. III. Synthese von Isoxazolo [3, 4-d] pyrimidinen,” Chemical and Pharmaceutical Bulletin, vol. 25, no. 11, pp. 2974–2982, 1977.
[29]
H. Griengl, E. Wanek, W. Schwarz, W. Streicher, B. Rosenwirth, and E. De Clercq, “2′-Fluorinated arabinonucleosides of 5-(2-haloalkyl)uracil: synthesis and antiviral activity,” Journal of Medicinal Chemistry, vol. 30, no. 7, pp. 1199–1204, 1987.
[30]
G. Shaw, Comprehensive Heterocyclic Chemistry, Volume 3, A. R. Katritzky, C.W. Rees, Eds., p. 57, Pergamon, Oxford, UK, 1984.
[31]
A. Agarwal and P. M. S. Chauhan, “Solid supported synthesis of structurally diverse dihydropyrido[2,3-d] pyrimidines using microwave irradiation,” Tetrahedron Letters, vol. 46, no. 8, pp. 1345–1348, 2005.
[32]
G. H. Mahdavinia, S. Rostamizadeh, A. M. Amani, and Z. Emdadi, “Ultrasound-promoted greener synthesis of aryl-14-H-dibenzo[a,j]xanthenes catalyzed by NH4H2PO4/SiO2 in water,” Ultrasonics Sonochemistry, vol. 16, no. 1, pp. 7–10, 2009.
[33]
G. Cravotto and P. Cintas, “Power ultrasound in organic synthesis: moving cavitational chemistry from academia to innovative and large-scale applications,” Chemical Society Reviews, vol. 35, no. 2, pp. 180–196, 2006.
[34]
T. J. Mason and J. P. Lorimer, Applied Sonochemistry: The Uses of Power Ultrasound in Chemistry and Processing, Wiley-VCH, 2002.
[35]
D. Mantu, C. Moldoveanu, A. Nicolescu, C. Deleanu, and I. I. Mangalagiu, “A facile synthesis of pyridazinone derivatives under ultrasonic irradiation,” Ultrasonics Sonochemistry, vol. 16, no. 4, pp. 452–454, 2009.
[36]
J. T. Li, Y. Yin, L. Li, and M. X. Sun, “A convenient and efficient protocol for the synthesis of 5-aryl-1,3-diphenylpyrazole catalyzed by hydrochloric acid under ultrasound irradiation,” Ultrasonics Sonochemistry, vol. 17, no. 1, pp. 11–13, 2010.
[37]
L. Pizzuti, P. L. G. Martins, B. A. Ribeiro et al., “Efficient sonochemical synthesis of novel 3,5-diaryl-4,5-dihydro-1H-pyrazole-1-carboximidamides,” Ultrasonics Sonochemistry, vol. 17, no. 1, pp. 34–37, 2010.
[38]
C.-L. Ni, X.-H. Song, H. Yan, X.-Q. Song, and R.-G. Zhong, “Improved synthesis of diethyl 2,6-dimethyl-4-aryl-4H-pyran-3,5-dicarboxylate under ultrasound irradiation,” Ultrasonics Sonochemistry, vol. 17, no. 2, pp. 367–369, 2010.
[39]
A. Bazgir, S. Ahadi, R. Ghahremanzadeh, H. R. Khavasi, and P. Mirzaei, “Ultrasound-assisted one-pot, three-component synthesis of spiro[indoline-3,4′-pyrazolo[3,4-b]pyridine]-2,6′(1′H)-diones in water,” Ultrasonics Sonochemistry, vol. 17, no. 2, pp. 447–452, 2010.
[40]
Z.-H. Zhang, J.-J. Li, and T.-S. Li, “Ultrasound-assisted synthesis of pyrroles catalyzed by zirconium chloride under solvent-free conditions,” Ultrasonics Sonochemistry, vol. 15, no. 5, pp. 673–676, 2008.
[41]
A. R. Khosropour, “Ultrasound-promoted greener synthesis of 2,4,5-trisubstituted imidazoles catalyzed by Zr(acac)4 under ambient conditions,” Ultrasonics Sonochemistry, vol. 15, no. 5, pp. 659–664, 2008.
[42]
R. H. Nia, M. Mamaghani, F. Shirini, and K. Tabatabaeian, “A convenient one-pot three-component approach for regioselective synthesis of novel substituted pyrazolo[1,5-a]pyrimidines using Fe+3-montmorillonite as efficient catalyst,” Journal of Heterocyclic Chemistry, vol. 51, no. 2, pp. 363–367, 2014.
[43]
M. Mamaghani, F. Shirini, N. O. Mahmoodi, A. Azimi-Roshan, and A. Monfared, “‘on water’ organic synthesis: three-component one-pot synthesis of novel bis(1-(cyclohexylamino)-1-oxoalkyl or aryl) fumarates,” Journal of the Iranian Chemical Society, vol. 11, no. 3, pp. 659–664, 2014.
[44]
M. Mamaghani, F. Shirini, N. O. Mahmoodi, A. Azimi-Roshan, and H. Hashemlou, “A green, efficient and recyclable Fe+3@K10 catalyst for the synthesis of bioactive pyrazolo[3,4-b]pyridin-6(7H)-ones under “on water” conditions,” Journal of Molecular Structure, vol. 1051, pp. 169–176, 2013.
[45]
R. Hossein Nia, M. Mamaghani, K. Tabatabaeian, F. Shirini, and M. Rassa, “An expeditious regioselective synthesis of novel bioactive indole-substituted chromene derivatives via one-pot three-component reaction,” Bioorganic and Medicinal Chemistry Letters, vol. 22, no. 18, pp. 5956–5960, 2012.
[46]
M. Mamaghani, A. Loghmanifar, and M. R. Taati, “An efficient one-pot synthesis of new 2-imino-1,3-thiazolidin-4-ones under ultrasonic conditions,” Ultrasonics Sonochemistry, vol. 18, no. 1, pp. 45–48, 2011.
[47]
M. Nikpassand, M. Mamaghani, F. Shirini, and K. Tabatabaeian, “A convenient ultrasound-promoted regioselective synthesis of fused polycyclic 4-aryl-3-methyl-4,7-dihydro-1H-pyrazolo[3,4-b]pyridines,” Ultrasonics Sonochemistry, vol. 17, no. 2, pp. 301–305, 2010.
[48]
M. Mamaghani, N. O. Mahmoodi, F. Shirini, A. Azimi-Roshan, and A. Monfared, “On water sonochemical multicomponent synthesis of novel bioactive 1,1′-(Aryl)bis(2-(cyclohexylamino)-2-oxoethane-1,1-diyl) Di(alkanoates and benzoates),” Journal of Chemistry, vol. 2013, Article ID 125959, 8 pages, 2013.
[49]
P. Crepaldi, B. Cacciari, M.-C. Bonache, et al., “6-Amino-2-mercapto-3H-pyrimidin-4-one derivatives as new candidates for the antagonism at the P2Y12 receptors,” Bioorganic & Medicinal Chemistry, vol. 17, no. 13, pp. 4612–4621, 2009.
