Efficient Syntheses of Ethyl 2-Methylthio- and Ethyl 2-Benzylthio-6-methyl(aryl)pyrimidine-4-carboxylates and Their Carboxylic Acid Derivatives

Nilo Zanatta; Andressa S. Fortes; Carlos E. Bencke; Mário A. Marangoni; Adriano F. Camargo; Cassio A. Fantinel; Helio G. Bonacorso; Marcos A. P. Martins

doi:10.1055/s-0034-1379696

Synthesis, Inhaltsverzeichnis

Synthesis 2015; 47(06): 827-835
DOI: 10.1055/s-0034-1379696

paper

Efficient Syntheses of Ethyl 2-Methylthio- and Ethyl 2-Benzylthio-6-methyl(aryl)pyrimidine-4-carboxylates and Their Carboxylic Acid Derivatives

Authors

Nilo Zanatta*

Núcleo de Química de Heterociclos (NUQUIMHE), Departamento de Química, Universidade Federal de Santa Maria, 97105-900, Santa Maria, Brazil eMail: nilo.zanatta@ufsm.br
Andressa S. Fortes

Núcleo de Química de Heterociclos (NUQUIMHE), Departamento de Química, Universidade Federal de Santa Maria, 97105-900, Santa Maria, Brazil eMail: nilo.zanatta@ufsm.br
Carlos E. Bencke

Núcleo de Química de Heterociclos (NUQUIMHE), Departamento de Química, Universidade Federal de Santa Maria, 97105-900, Santa Maria, Brazil eMail: nilo.zanatta@ufsm.br
Mário A. Marangoni

Núcleo de Química de Heterociclos (NUQUIMHE), Departamento de Química, Universidade Federal de Santa Maria, 97105-900, Santa Maria, Brazil eMail: nilo.zanatta@ufsm.br
Adriano F. Camargo

Núcleo de Química de Heterociclos (NUQUIMHE), Departamento de Química, Universidade Federal de Santa Maria, 97105-900, Santa Maria, Brazil eMail: nilo.zanatta@ufsm.br
Cassio A. Fantinel

Núcleo de Química de Heterociclos (NUQUIMHE), Departamento de Química, Universidade Federal de Santa Maria, 97105-900, Santa Maria, Brazil eMail: nilo.zanatta@ufsm.br
Helio G. Bonacorso

Núcleo de Química de Heterociclos (NUQUIMHE), Departamento de Química, Universidade Federal de Santa Maria, 97105-900, Santa Maria, Brazil eMail: nilo.zanatta@ufsm.br
Marcos A. P. Martins

Núcleo de Química de Heterociclos (NUQUIMHE), Departamento de Química, Universidade Federal de Santa Maria, 97105-900, Santa Maria, Brazil eMail: nilo.zanatta@ufsm.br

Abstract

Alle Artikel dieser Rubrik

Abstract

A simple and efficient procedure for the synthesis of ethyl 2-methylthio- and ethyl 2-benzylthio-6-methyl(aryl)-pyrimidine-4-carboxylates and their corresponding acid derivatives is reported. The products are obtained in good yields via the cyclocondensation reaction of ethyl 4-alkoxy-2-oxo-4-methyl(aryl)-but-3-enoates with 2-methylisothiourea sulfate or 2-benzylisothiourea hydrochloride, under mild, basic, aqueous conditions.

Key words

2,4,6-trisubstituted pyrimidines - 2-thiopyrimidines - ethyl pyrimidine-4-carboxylates - pyrimidine-4-carboxylic acids - cyclocondensation

Volltext

Referenzen

References
1 Agarwal A, Srivastava K, Puri SK, Chauhana PM. S. Bioorg. Med. Chem. 2005; 13: 4645
2 Bailey JP, Giles MB, Pass M. WO 2006005914 A1, 2006 ; Chem. Abstr. 2006, 144, 150379.
3 Rotili D, Tarantino D, Artico M, Nawrozkij MB, Ortega EG, Clotet B, Samuele A, Esté JA, Maga G, Mail A. J. Med. Chem. 2011; 54: 3091
4 Agarwal A, Srivastava K, Puri SK, Sinha S, Chauhana PM. S. Bioorg. Med. Chem. Lett. 2005; 15: 5218

5a Skulnik HI, Ludens JH, Wendling MG, Glenn EM, Rohloff NA, Smith RJ, Wierenga W. J. Med. Chem. 1986; 29: 1499
5b Kawauchi K, Fukazawa N, Ishibashi D, Yano O, Iwata D, Etatsugu H, Sobashima T. JP 06172377, 1994 ; Chem. Abstr. 1995, 123, 33585f
5c Magnus A, Confalone PN, Storace L. Tetrahedron Lett. 2000; 41: 3015

6a Pees K, Liers P, Karla C. EP 834513, 1998 ; Chem. Abstr. 1998, 128, 257444a.
6b Drewes MW, Andree R, Dollinger M. WO 9854155, 1999 ; Chem. Abstr. 1999, 130, 38393w.
6c Ishii S, Akimoto K, Nakayama K, Yagi K, Ooya E, Umehara T, Kudo M, Inoe Y. JP 0543555, 1993 ; Chem. Abstr. 1993, 119, 180804x.
6d Inoue Y, Kobayashi T, Masu A, Asahina K. JP 03197467, 1991 ; Chem. Abstr. 1991, 115, 280054p.
6e Djuric SW, BaMaung NY, Basha A, Liu H, Luly JR, Madar DJ, Sciotti RJ, Tu NP, Wagenaar FL, Wiedeman PE, Zhou X, Ballaron S, Bauch J, Chen Y, Chiou XG, Fey T, Gauvin D, Gubbins E, Hsieh GC, Marsh KC, Mollison KW, Pong M, Shaughnessy TK, Sheets MP, Smith M, Trevillyan JM, Warrior U, Wegner CD, Carter GW. J. Med. Chem. 2000; 43: 2975

7 Xu X, Xu J, Xiau L, Peng X, Shi Y, Ma R, Chen S, Li G. CN 101255137 A, 2008 ; Chem. Abstr. 2008, 149, 378750.
8 Matsushita A, Yoshii K, Oue M, Nakamura T, Yamada S. US 20030055252 A1, 2003 ; Chem. Abstr. 2003, 138, 238198.

9a Kim C.-H, Marquez VE, Mao DT, Haines DR, McCormack JJ. J. Med. Chem. 1986; 29: 1374
9b Liverton NJ, Butcher JW, McIntyre CJ, Claiborne CF, Claremon DA, McCauley JA, Romano JJ, Thompson W, Munson PM. US 2003119811 A1, 2003 ; Chem. Abstr. 2002, 137, 310932.

10 Grima PP. M, Karstens WF. J, Timmers CM. WO 2006117368 A1, 2006 ; Chem. Abstr. 2006, 145, 489143.
11 Haddida Ruah SS, Hazlewood AR, Grooten-Huis PD. J, Sing AK, Cleveland T, van Goor F. WO 2006127588 A2, 2006 ; Chem. Abstr. 2006, 146, 27856.
12 Bolli M, Lescop C, Mathys B, Mueller C, Nayler O, Steiner B. WO 2009057079 A2, 2009 ; Chem. Abstr. 2009, 150, 515194.
13 Piotrowski DW, Futatsugi K, Warmus JS, Orr ST. M, Freeman-Cook KD, Londregan AT, Wei L, Jennings SM, Herr M, Coffey SB, Jiao W, Storer G, Hepworth D, Wang J, Lavergne SY, Chin JE, Hadcock JR, Brenner MB, Wolford AC, Janssen AM, Roush NS, Buxton J, Hinchey T, Kalgutkar AS, Sharma R, Flynn DA. ACS Med. Chem. Lett. 2013; 4: 63
14 Leprêtre A, Turck A, Plé A, Knochel P, Quéguiner G. Tetrahedron 2000; 56: 265
15 Obrecht D, Ermert P, Luther A, Eberle M, Bachmann F. WO 200487679 A1, 2004 ; Chem. Abstr. 2004, 141, 350188.
16 Clark MP, Laughlin SK, Laufersweiler MJ, Bookland RG, Brugel TA, Golebiowski A, Sabat MP, Townes JA, van Rens JC, Djung JF, Natchus MG, De B, Hsieh LC, Xu SC, Walter RL, Mekel MJ, Heitmeyer SA, Brown KK, Juergens K, Taiwo YO, Janusz MJ. J. Med. Chem. 2004; 47: 2724
17 Kim JY, Kim D, Kang SY, Park W.-K, Kim HJ, Jung ME, Son E.-J, Pae AN, Kim J, Lee J. Bioorg. Med. Chem. Lett. 2010; 20: 6439

18a Druzhinin SV, Balenkova ES, Nenajdenko VG. Tetrahedron 2007; 63: 7753
18b Martins MA. P, Cunico W, Pereira CM. P, Sinhorin AP, Flores AF. C, Bonacorso HG, Zanatta N. Curr. Org. Synth. 2004; 1: 391

19a Machado P, Rosa FA, Rossatto M, Sant’Anna GS, Sauzem PD, Silva RM. S, Rubin MA, Ferreira J, Bonacorso HG, Zanatta N, Martins MA. P. ARKIVOC 2007; (xvi): 281
19b Machado P, Lima GR, Rotta M, Bonacorso HG, Zanatta N, Martins MA. P. Ultrason. Sonochem. 2011; 18: 293
19c Stepaniuk OO, Matviienko O, Kondratov IS, Vitruk IV, Tolmachev AO. Synthesis 2013; 45: 925

20a Boyer J, Arnoult E, Médebielle M, Guillemont J, Unge J, Jochmans D. J. Med. Chem. 2011; 54: 7974
20b Summa V, Petrocchi A, Matassa VG, Taliani M, Laufer R, De Francesco R, Altamura S, Pacel P. J. Med. Chem. 2004; 47: 5336
20c Crescenzi B, Poma M, Ontoria JM, Marchetti A, Nizi E, Matassa VG, Gardelli C. Lett. Drug Des. Discovery 2005; 2: 451
20d Ponzi S, Giuliano C, Donghi M, Poma M, Matassa VG, Stansfield I. Lett. Drug Des. Discovery 2005; 2: 456
20e Stansfield I, Avolio S, Colarusso S, Gennari N, Narjes F, Pacini B, Ponzi S, Harper S. Bioorg. Med. Chem. Lett. 2004; 14: 5085
20f Radi M, Dreassi E, Brullo C, Crespan E, Tintori C, Bernardo V, Valoti M, Zamperini C, Daigl H, Musumeci F, Carraro F, Naldini A, Filippi I, Maga G, Schenone S, Botta M. J. Med. Chem. 2011; 54: 2610
20g Hieke M, Greiner C, Dittrich M, Reisen F, Schneider G, Zsilavecz MS, Werz O. J. Med. Chem. 2011; 54: 4490
20h Chang LC. W, Spanjersberg RF, von Frijtag Drabbe Künzel JK, Mulder-Krieger T, van den Hout G, Beukers MW, Brussee J, IJzerman AP. J. Med. Chem. 2004; 47: 6529
20i Nugent RA, Schlachter ST, Murphy MJ, Cleek GJ, Poel TJ, Wishka DG, Graber DR, Yagi Y, Keiser BJ, Olmsted RA, Kopta LA, Swaney SM, Poppe SM, Morris J, Tarpley WG, Thomas RC. J. Med. Chem. 1998; 41: 3793
20j Jonak JP, Mead LH, Ho YK, Zakrzewski SF. J. Med. Chem. 1873; 16: 724

21 Petricci E, Mugnaini C, Radi M, Togninelli A, Bernardi C, Manetti F, Parlato MC, Renzulli ML, Alongi M, Falciani C, Corelli F, Botta M. ARKIVOC 2006; (vii): 452
22 Zanatta N, Flores DC, Madruga CC, Faoro D, Flores AF. C, Bonacorso HG, Martins MA. P. Synthesis 2003; 894
23 Nilsson LI, Ertan A, Eeigelt D, Nolsöe JM. J. J. Heterocycl. Chem. 2010; 47: 887

24a Khan S, Tyagi V, Mahar R, Kumar B, Chauhan PM. S. Synthesis 2013; 45: 2405
24b Badawey E.-SA. M. J. Heterocycl. Chem. 1996; 33: 229

25 Bossahard HH, Mary R, Schmid M, Zollinger H. Helv. Chim. Acta 1959; 42: 1659
26 Zanatta N, Cortelini MF. M, Carpes MJ. S, Bonacorso HG, Martins MA. P. J. Heterocycl. Chem. 1997; 34: 509