An Efficient One-Pot Three-Component Synthesis of Novel Quinazoline-4-Carboxylic Acid and Its Ester and Amide Derivatives

Year 2022, Volume: 50 Issue: 4, 377 - 386, 09.10.2022

Derviş Gök

https://doi.org/10.15671/hjbc.1004758

Abstract

A series of novel quinazoline derivatives, which may be drug candidates, were synthesized, and their structures were characterized by IR, 1H NMR, 13C NMR and Q-TOF LC/MS spectrometry. First, 2-(4-chloro-phenyl)-quinazoline-4-carboxylic acid (2) was synthesized from a one-pot three-component condensation reaction of (2-amino-phenyl)-oxo-acetic acid sodium salt obtained from alkaline hydrolysis of isatin (indole-2,3-dione) with 4-chlorobenzaldehyde and ammonium acetate. The carboxylic acid compound 2 allowed the synthesis of the ester, acid chloride and amide derivatives. New quinazoline ester derivatives (3-6, 8) were synthesized by the reactions of compound 2 and various alcohols. Quinazoline amide derivatives (9-13) were then obtained from the reaction of different aliphatic and aromatic amines and 2-(4-chloro-phenyl)-quinazoline-4-carbonyl chloride (7) formed from the reaction of SOCl2 and compound 2.

Keywords

Isatin, quinazoline-4-carboxylic acid, amide, ester

Supporting Institution

Kütahya Dumlupınar University Technology Research Fund

Project Number

No, 2015/24

Thanks

The author thank the Kütahya Dumlupınar University Technology Research Fund for supporting this study with a scientific research project (No, 2015/24).

Bir Etkili Tek Ortamda Üç Bileşenli Yeni Kinazolin-4-Karboksilik Asit ve Onun Ester ve Amit Türevlerinin Sentezi

Abstract

İlaç adayları olabilecek bir dizi yeni kinazolin türevleri sentezlendi ve yapıları IR, 1H NMR, 13C NMR ve Q-TOF LC/MS spektrometresi ile karakterize edildi. Önce amonyum asetat ve 4-klorobenzaldehit ile isatinin (indol-2,3-dion) hidrolizinden elde edilen (2-amino-fenil)-okso-asetik asit sodyum tuzunun aynı ortamda üç bileşenli kondenzasyon reaksiyonundan 2-(4-kloro-fenil)-kinazolin-4-karboksilik asit (2) sentezlendi. Karboksilik asit bileşiği 2, ester, asit klorür ve amit türevlerinin sentezine izin verdi. Yeni kinazolin ester türevleri (3-6, 8), 2 bileşiği ve çeşitli alkollerin reaksiyonlarından sentezlendi. Daha sonra kinazolin amit türevleri (9-13), çeşitli alifatik ve aromatik aminlerin 2 bileşiği ve SOCl2’ün reaksiyonundan oluşan 2-(4-kloro-fenil)-kinazolin-4-karbonil klorürün (7) reaksiyonundan elde edildi.

Keywords

İsatin, kinazolin-4-karboksilik asit, amit, ester

Project Number

No, 2015/24

References

• G.F. Xu, B.A. Song, P.S. Bhadury, S. Yang, P.Q. Zhang, L.H. Jin, W. Xue, D.Y. Hu, P. Lu, Synthesis and antifungal activity of novel s-substituted 6-fluoro-4-alkyl(aryl)thioquinazoline derivatives, Bioorgan Med Chem, 15 (2007) 3768-3774.
• J. Jampilek, R. Musiol, J. Finster, M. Pesko, J. Carroll, K. Kralova, M. Vejsova, J. O'Mahony, A. Coffey, J. Dohnal, J. Polanski, Investigating Biological Activity Spectrum for Novel Styrylquinazoline Analogues, Molecules, 14 (2009) 4246-4265.
• J. Odingo, T. O'Malley, E.A. Kesicki, T. Alling, M.A. Bailey, J. Early, J. Ollinger, S. Dalai, N. Kumar, R.V. Singh, P.A. Hipskind, J.W. Cramer, T. Ioerger, J. Sacchettini, R. Vickers, T. Parish, Synthesis and evaluation of the 2,4-diaminoquinazoline series as anti-tubercular agents, Bioorgan Med Chem, 22 (2014) 6965-6979.
• D. Giardina, D. Martarelli, G. Sagratini, P. Angeli, D. Ballinari, U. Gulini, C. Melchiorre, E. Poggesi, P. Pompei, Doxazosin-Related alpha(1)-Adrenoceptor Antagonists With Prostate Antitumor Activity, J Med Chem, 52 (2009) 4951-4954.
• C. Mendoza-Martinez, J. Correa-Basurto, R. Nieto-Meneses, A. Marquez-Navarro, R. Aguilar-Suarez, M.D. Montero-Cortes, B. Nogueda-Torres, E. Suarez-Contreras, N. Galindo-Sevilla, A. Rojas-Rojas, A. Rodriguez-Lezama, F. Hernandez-Luis, Design, synthesis and biological evaluation of quinazoline derivatives as anti-trypanosomatid and anti-plasmodial agents, Eur J Med Chem, 96 (2015) 296-307.
• H. Xiao, P. Li, D.Y. Hu, B.A. Song, Synthesis and anti-TMV activity of novel beta-amino acid ester derivatives containing quinazoline and benzothiazole moieties, Bioorg Med Chem Lett, 24 (2014) 3452-3454.
• E. Jafari, M.R. Khajouei, F. Hassanzadeh, G.H. Hakimelahi, G.A. Khodarahmi, Quinazolinone and quinazoline derivatives: recent structures with potent antimicrobial and cytotoxic activities, Res Pharm Sci, 11 (2016) 1-14.
• P. Verhaeghe, N. Azas, M. Gasquet, S. Hutter, C. Ducros, M. Laget, S. Rault, P. Rathelot, P. Vanelle, Synthesis and antiplasmodial activity of new 4-aryl-2-trichloromethylquinazolines, Bioorg Med Chem Lett, 18 (2008) 396-401.
• R.A. Smits, M. Adami, E.P. Istyastono, O.P. Zuiderveld, C.M.E. van Dam, F.J.J. de Kanter, A. Jongejan, G. Coruzzi, R. Leurs, I.J.P. de Esch, Synthesis and QSAR of Quinazoline Sulfonamides As Highly Potent Human Histamine H-4 Receptor Inverse Agonists, J Med Chem, 53 (2010) 2390-2400.
• V. Alagarsamy, U.S. Pathak, Synthesis and antihypertensive activity of novel 3-benzyl-2-substituted-3H-[1,2,4]triazolo[5,1-b]quinazolin-9-ones, Bioorgan Med Chem, 15 (2007) 3457-3462.
• M.S. Malamas, J. Millen, Quinazolineacetic Acids and Related Analogs as Aldose Reductase Inhibitors, J Med Chem, 34 (1991) 1492-1503.
• A. Rosowsky, J.E. Wright, C.M. Vaidya, R.A. Forsch, The effect of side-chain, para-aminobenzoyl region, and B-ring modifications on dihydrofolate reductase binding, influx via the reduced folate carrier, and cytotoxicity of the potent nonpolyglutamatable antifolate N-alpha-(4-amino-4-deoxypteroyl)-N-delta-hemiphthaloyl-L-ornithine, Pharmacol Therapeut, 85 (2000) 191-205.
• A.M.F. Kersemaekers, G.J. Fleuren, E.G. Kenter, L.J.C.M. Van den Broek, S.M. Uljee, J. Hermans, M.J. Van de Vijver, Oncogene alterations in carcinomas of the uterine cervix: Overexpression of the epidermal growth factor receptor is associated with poor prognosis, Clinical Cancer Research, 5 (1999) 577-586.
• D.W. Fry, A.J. Kraker, A. Mcmichael, L.A. Ambroso, J.M. Nelson, W.R. Leopold, R.W. Conners, A.J. Bridges, A Specific Inhibitor of the Epidermal Growth-Factor Receptor Tyrosine Kinase, Science, 265 (1994) 1093-1095.
• P. Chaturvedula, G.M. Dubowchik, A.P. Degan, X.J. Han, C.M. Conway, D. Cook, C. Davis, R. Denton, R. Macci, N.R. Mathias, S. Pin, L. Signor, G. Thalody, R. Schartman, K.A. Widmann, C. Xu, J.E. Macor, MEDI 220-Design and synthesis of potent cgrp antagonists for migraine, Abstr Pap Am Chem S, 234 (2007).
• J.P. Xu, X.Y. Liu, S. Yang, C.G. Zhang, L. Wang, Y.K. Shi, Icotinib as initial treatment in lung adenocarcinoma patients with brain metastases, Thoracic Cancer, 7 (2016) 437-441.
• J.A. Taylor, T.M. Twomey, M.S. von Wittenau, The metabolic fate of prazosin, Xenobiotica, 7 (1977) 357-364.
• D. Cameron, M. Casey, M. Press, D. Lindquist, T. Pienkowski, C.G. Romieu, S. Chan, A. Jagiello-Gruszfeld, B. Kaufman, J. Crown, A. Chan, M. Campone, P. Viens, N. Davidson, V. Gorbounova, J.I. Raats, D. Skarlos, B. Newstat, D. Roychowdhury, P. Paoletti, C. Oliva, S. Rubin, S. Stein, C.E. Geyer, A phase III randomized comparison of lapatinib plus capecitabine versus capecitabine alone in women with advanced breast cancer that has progressed on trastuzumab: updated efficacy and biomarker analyses, Breast Cancer Res Tr, 112 (2008) 533-543.
• R.T. Dungo, G.M. Keating, Afatinib: first global approval, Drugs, 73 (2013) 1503-1515.
• K.L. Reckamp, G. Giaccone, D.R. Camidge, S.M. Gadgeel, F.R. Khuri, J.A. Engelman, M. Koczywas, A. Rajan, A.K. Campbell, D. Gernhardt, A. Ruiz-Garcia, S. Letrent, J. Liang, I. Taylor, J.P. O'Connell, P.A. Janne, A phase 2 trial of dacomitinib (PF-00299804), an oral, irreversible pan-HER (human epidermal growth factor receptor) inhibitor, in patients with advanced non-small cell lung cancer after failure of prior chemotherapy and erlotinib, Cancer-Am Cancer Soc, 120 (2014) 1145-1154.
• B. Han, X.L. Yang, C. Wang, Y.W. Bai, T.C. Pan, X. Chen, W. Yu, CuCl/DABCO/4-HO-TEMPO-Catalyzed Aerobic Oxidative Synthesis of 2-Substituted Quinazolines and 4H-3,1-Benzoxazines, J Org Chem, 77 (2012) 1136-1142.
• V.L. Truong, M. Morrow, Mild and efficient ligand-free copper-catalyzed condensation for the synthesis of quinazolines, Tetrahedron Lett, 51 (2010) 758-760.
• Z.Y. Chen, J.X. Chen, M.C. Liu, J.C. Ding, W.X. Gao, X.B. Huang, H.Y. Wu, Unexpected Copper-Catalyzed Cascade Synthesis of Quinazoline Derivatives, J Org Chem, 78 (2013) 11342-11348.
• J.T. Zhang, C.M. Yu, S.J. Wang, C.F. Wan, Z.Y. Wang, A novel and efficient methodology for the construction of quinazolines based on supported copper oxide nanoparticles, Chem Commun, 46 (2010) 5244-5246.
• C. Wang, S.F. Li, H.X. Liu, Y.Y. Jiang, H. Fu, Copper-Catalyzed Synthesis of Quinazoline Derivatives via Ullmann-Type Coupling and Aerobic Oxidation, J Org Chem, 75 (2010) 7936-7938.
• R. Sarma, D. Prajapati, Microwave-promoted efficient synthesis of dihydroquinazolines, Green Chem, 13 (2011) 718-722.
• D. Gok, One-pot three-component synthesis of novel 2-(3-nitro-phenyl)-quinazoline-4-carboxylic acid derivatives, J Heterocyclic Chem, 56 (2019) 3343-3353.
• C. Derabli, R. Boulcina, G. Kirsch, B. Carboni, A. Debache, A DMAP-catalyzed mild and efficient synthesis of 1,2-dihydroquinazolines via a one-pot three-component protocol, Tetrahedron Lett, 55 (2014) 200-204.