One-Pot, Three-Component Synthesis of Novel 4-Phenyl-2-[3-(alkynyl/alkenyl/aryl)phenyl]pyrimidine Libraries via Michael Addition, Cyclization, and C–C Coupling Reactions: A New MCR Strategy

L. Srinivasula Reddy; T. Ram Reddy; N. C. Gangi Reddy; Reddy Bodireddy Mohan; Y. Lingappa

doi:10.1055/s-0032-1316814

Synthesis, Inhaltsverzeichnis

Synthesis 2013; 45(1): 75-84
DOI: 10.1055/s-0032-1316814

paper

One-Pot, Three-Component Synthesis of Novel 4-Phenyl-2-[3-(alkynyl/alkenyl/aryl)phenyl]pyrimidine Libraries via Michael Addition, Cyclization, and C–C Coupling Reactions: A New MCR Strategy

L. Srinivasula Reddy

^aDepartment of Chemistry, Sri Venkateswara University, Tirupati 517 502, Andhra Pradesh, India

^bDr. Reddy’s Laboratories Limited, Bollaram Road, Miyapur, Hyderabad 500 049, Andhra Pradesh, India

,

T. Ram Reddy

^bDr. Reddy’s Laboratories Limited, Bollaram Road, Miyapur, Hyderabad 500 049, Andhra Pradesh, India

,

N. C. Gangi Reddy*

^cDepartment of Chemistry, School of Physical Sciences, Yogi Vemana University, Kadapa 516 003, Andhra Pradesh, India eMail: ncgreddy@yogivemanauniversity.ac.in

,

Reddy Bodireddy Mohan

^cDepartment of Chemistry, School of Physical Sciences, Yogi Vemana University, Kadapa 516 003, Andhra Pradesh, India eMail: ncgreddy@yogivemanauniversity.ac.in

,

Y. Lingappa

^aDepartment of Chemistry, Sri Venkateswara University, Tirupati 517 502, Andhra Pradesh, India

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Abstract

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Abstract

Privileged medicinal scaffolds based on the structures of 4-phenyl-2-[3-(alkynyl/alkenyl/aryl)phenyl]-substituted pyrimidines have been synthesized via a single-step, three-component reaction of 3-(dimethylamino)-1-phenylprop-2-en-1-one (enaminone), 3-bromobenzimidamide hydrochloride, and various alkynes/alkenes/arylboronic acids. The mechanism of this multi-component reaction (MCR) involves a Michael addition, cyclization, isomerization, and dehydration, followed by Sonogashira, Heck or Suzuki coupling. This new MCR strategy afforded a new compound library based on pyrimidine framework.

Key words

multi-component reactions (MCRs) - Michael addition - Pd catalyst - C–C coupling reactions

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References

The term ‘privileged scaffolds or structures’ was originally introduced by Merck researchers in their work on benzodiazepines:

1a Evans BE, Rittle KE, Bock MG, DiPardo RM, Freidinger RM, Whitter WL, Lundell GF, Veber DF, Anderson PS. J. Med. Chem. 1988; 31: 2235
1b Patchett AA, Nargund RP. Ann. Rep. Med. Chem. 2000; 35: 289

2a Press JB, McNally JJ, Keiser JA, Offord SJ, Katz LB, Giardino E, Falotico R, Tobia AJ. Eur. J. Med. Chem. 1989; 24: 627
2b Alam O, Khan SA, Siddiqui N, Ahsan W, Verma SP, Gilani SJ. Eur. J. Med. Chem. 2010; 45: 5113
2c Amin KM, Awadalla FM, Eissa AA. M, Abou-Seri SM, Hassan GS. Bioorg. Med. Chem. 2011; 19: 6087

3a Bruno O, Schenone S, Ranise A, Barocelli E, Chiavarini M, Ballabeni V, Bertoni S. Arzneim.-Forsch./Drug Res. 2000; 50: 140
3b Bruno O, Brullo C, Schenone S, Bondavalli F, Ranise A, Tognolini M, Ballabeni V, Barocelli E. Bioorg. Med. Chem. 2004; 12: 553

4 Wyrzykiewicz E, Bartkowiak G, Kedzia B. Farmaco 1993; 48: 979
5 Sharma P, Rane N, Gurram VK. Bioorg. Med. Chem. Lett. 2004; 14: 4185
6 Elkholy YM, Morsy MA. Molecules 2006; 11: 890
7 Holla BS, Mahalinga M, Karthikeyan MS, Akberali PM, Shetty NS. Bioorg. Med. Chem. 2006; 14: 2040
8 Ingarsal N, Saravanan G, Amutha P, Nagarajan S. Eur. J. Med. Chem. 2007; 42: 517
9 Zhao X.-L, Zhao Y.-F, Guo S.-C, Song H.-S, Wang D, Gong P. Molecules 2007; 12: 1136
10 Cordeu L, Cubedo E, Bandrés E, Rebollo A, Sáenz X, Chozas H, Domínguez MV, Echeverría M, Mendivil B, Sanmartin C, Palop JA, Font M, García-Foncillas J. Bioorg. Med. Chem. 2007; 15: 1659
11 Sondhi SM, Singh N, Johar M, Kumar A. Bioorg. Med. Chem. 2005; 13: 6158
12 Amin KM, Hanna MM, Abo-Youssef HE, George RF. Eur. J. Med. Chem. 2009; 44: 4572

13a Baumgarth M, Beier N, Gericke R. J. Med. Chem. 1997; 40: 2017
13b Ramesh LS, Varsha IS, Ganesh DJ, Jyoti BW. Med. Chem. Res. 2012; 21: 1825

14 Nega S, Aionso J, Diazj A, Junquere F. J. Heterocycl. Chem. 1990; 27: 269
15 Shishoo CJ, Jain KS. J. Heterocycl. Chem. 1992; 29: 883
16 Peters JU, Hunziker D, Fischer H, Kansy M, Weber S, Kritter S, Muller A, Ricklin F, Boehringer M, Poli SM, Csato M, Loeffler BM. Bioorg. Med. Chem. Lett. 2004; 14: 3575
17 Peters JU, Weber S, Kritter S, Weiss P, Wallier A, Zimmerli D, Boehringer M, Steger M, Loeffler BM. Bioorg. Med. Chem. Lett. 2004; 14: 3579

For reviews, see:

18a Undheim K, Benneche T In Comprehensive Heterocyclic Chemistry II . Vol. 6. Katritzky AR, Rees CW, Scriven EF. V, McKillop A. Pergamon; Oxford: 1996: 93
18b Lagoja IM. Chem. Biodiversity 2005; 2: 1
18c Michael JP. Nat. Prod. Rep. 2005; 22: 627
18d Joule JA, Mills KI. Heterocyclic Chemistry . 4th ed. Blackwell Science Ltd; Cambridge: 2000: 194
18e Hill MD, Movassaghi M. Chem.–Eur. J. 2008; 14: 6836

For reviews, see:

19a Turck A, Ple N, Mongin F, Queguiner G. Tetrahedron 2001; 57: 4489
19b Chinchilla R, Najera C, Yus M. Chem. Rev. 2004; 104: 2667
19c Schroder S, Stock C, Bach T. Tetrahedron 2005; 61: 2245
19d Martin R, Buchwald SL. Acc. Chem. Res. 2008; 41: 1461
19e Surry DS, Buchwald SL. Angew. Chem. Int. Ed. 2008; 47: 6338

Passerini three-component and Ugi four-component condensations are the most popular among many other reactions for their wide scope and synthetic utility. For reviews, see:

20a Bienayme H, Hulme C, Oddon G, Schmitt P. Chem. Eur. J. 2000; 6: 3321
20b Dömling A, Ugi I. Angew. Chem. Int. Ed. 2000; 39: 3168

For recent reviews, see:

21a Toure BB, Hall DG. Chem. Rev. 2009; 109: 4439
21b Balme G, Bossharth E, Monteiro N. Eur. J. Org. Chem. 2003; 4101
21c Hulme C, Gore V. Curr. Med. Chem. 2003; 1051
21d Zhu J. Eur. J. Org. Chem. 2003; 1133

22 Weber L, Illgen K, Almstetter M. Synlett 1999; 366

23a Lin Y-i, Lang SA. Jr. J. Heterocycl. Chem. 1977; 14: 345
23b Bredereck H, Effenberger F, Botsch H. Chem. Ber. 1964; 97: 3397
23c Junek H, Schmidt A. Monatsh. Chem. 1968; 99: 635
23d Junek H, Stolz G. Monatsh. Chem. 1970; 201: 1234

24 Medwid JB, Rolf P, Baker JS, Brockman JA, Du MT, Hallett WA, Hanifin WJ, Hardy RA, Ernestine TM. Jr, Torley LW, Wren S. J. Med. Chem. 1990; 33: 1230

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