Synthesis and Characterization
of Substituted Pyrazino[2′,3′:4,5]thieno[3,2-d]pyrimidines and Related Molecules

Antonio Fernández-Mato; Carlos Peinador; José M. Quintela

doi:10.1055/s-0030-1258432

PAPER

Synthesis and Characterization of Substituted Pyrazino[2′,3′:4,5]thieno[3,2-d]pyrimidines and Related Molecules

Antonio Fernández-Mato, Carlos Peinador*, José M. Quintela*
Departamento de Química Fundamental, Facultad de Ciencias, Universidade da Coruña, Campus A Zapateira, A Coruña 15008, Spain
Fax: +34(981)167065; e-Mail: carlos.peinador@udc.es; e-Mail: jose.maria.quintela@udc.es;

Abstract

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Abstract

An efficient access for the synthesis of substituted pyrazino[2′,3′:4,5]thieno[3,2-d]pyrimidines and pyrazino[2′,3′:4,5]thieno[3,2-d]-1,2,3-triazines, heteroaromatic nitrogen ligands, is reported. The title compounds were obtained by functionalization of the corresponding chloro precursors, synthesized by reaction between 7-aminothieno[2,3-b]pyrazine-6-carbonitrile and N,N-dimethyldichloromethyleniminium chloride (Viehe’s salt) or sodium nitrite/hydrochloric acid, respectively. Moreover, this procedure provided a convenient synthetic route to bis(pyrazino[2′,3′:4,5]thieno[3,2-d]pyrimidines), functionalized molecules that are not readily available by other synthetic methods.

Key words

heterocycles - ligands - ring closure - antitumor agents - fused-ring systems

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References

<A NAME="RT53410SS-1A">1a</A> Pitt RW. Parry DM. Perry BG. Groom CR.
J. Med. Chem. 2009, 52: 2952

<A NAME="RT53410SS-1B">1b</A> Carr RAE. Congreve M. Murray CW. Rees DC. Drug Discovery Today 2005, 10: 987

For recent contributions, see:

<A NAME="RT53410SS-2A">2a</A> Haraguchi K. Kubota Y. Tanaka H. J. Org. Chem. 2004, 69: 1831

<A NAME="RT53410SS-2B">2b</A> Depecker G. Patino N. Giorgio CD. Terreux R. Cabrol-Bass D. Bailly C. Aubertin A.-M. Condom R. Org. Biomol. Chem. 2004, 2: 74

<A NAME="RT53410SS-3A">3a</A> Palacios F. Alonso C. Amezua P. Rubiales G. J. Org. Chem. 2002, 67: 1941 ; and references cited therein

<A NAME="RT53410SS-3B">3b</A> Renslo AR. Danheiser RL. J. Org. Chem. 1998, 63: 7840

<A NAME="RT53410SS-3C">3c</A> Neuschütz K. Velker J. Neier R. Synthesis 1998, 227

<A NAME="RT53410SS-3D">3d</A> Ihara M. Fukumoto K. Nat. Prod. Rep. 1997, 14: 413

<A NAME="RT53410SS-3E">3e</A> Taylor EC. Dowling JE. J. Org. Chem. 1997, 62: 1599 ; and pertinent references cited therein

<A NAME="RT53410SS-3F">3f</A> Jones G. In Comprehensive Heterocyclic Chemistry II Vol. 5: Katritzky AR. Rees CW. Scriven EFV. McKillop A. Pergamon; Oxford: 1996.

<A NAME="RT53410SS-3G">3g</A> Oikawa T. Kanomata N. Tada M. J. Org. Chem. 1993, 58: 2046

For examples, see:

<A NAME="RT53410SS-4A">4a</A> Chambhare RV. Khadse BG. Bobde AS. Bahekar RH. Eur. J. Med. Chem. 2003, 38: 89

<A NAME="RT53410SS-4B">4b</A> Sishoo CJ. Shirsath VS. Rathod IS. Yande VD. Eur. J. Med. Chem. 2000, 35: 351

<A NAME="RT53410SS-4C">4c</A> Walter H. inventors; WO 9,914,202. ; Chem. Abstr. 1999, 130, 252368k

<A NAME="RT53410SS-4D">4d</A> Varvounis G. Giannopoulos T. Adv. Heterocycl. Chem. 1996, 66: 193

For recent reviews on the synthesis, properties and biological activity of thienopyridines, see:

<A NAME="RT53410SS-4E">4e</A> Backhite EA.-G. Phosphorus, Sulfur Silicon Relat. Elem. 2003, 178: 929

<A NAME="RT53410SS-4F">4f</A> Litvinov VP. Dotsenko VV. Krivokolysko SG. Russ. Chem. Bull. 2005, 54: 864

<A NAME="RT53410SS-5A">5a</A> Quintela JM. González L. Devesa I. Ferrándiz ML. Alcaraz MJ. Riguera R. Bioorg. Med. Chem. 2003, 11: 863

<A NAME="RT53410SS-5B">5b</A> Quintela JM. Peinador C. Moreira MJ. Alfonso A. Botana LM. Riguera R. Eur. J. Med. Chem. 2001, 36: 321

<A NAME="RT53410SS-5C">5c</A> Quintela JM. Peinador C. Veiga C. González L. Botana LM. Alfonso A. Riguera R. Bioorg. Med. Chem. 1998, 6: 1911

<A NAME="RT53410SS-6A">6a</A> Martínez-Poveda B. Muñoz-Chápuli R. Rodríguez-Nieto S. Quintela JM. Fernndez A. Medina MA. Quesada AR. Mol. Cancer Ther. 2007, 6: 2675

<A NAME="RT53410SS-6B">6b</A> Rioja I. Ubeda A. Terencio MC. Guillén I. Riguera R. Quintela JM. Peinador C. González L. Alcaraz MJ. Eur. J. Pharmacol. 2000, 397: 207

<A NAME="RT53410SS-6C">6c</A> Quintela JM. Peinador C. González LM. Rioja I. Terencio MC. Ubeda A. Alcaraz MJ. Riguera R. J. Med. Chem. 1999, 42: 4720

<A NAME="RT53410SS-7">7</A> Quintela JM. Peinador C. González L. Iglesias R. Paramá A. Alvarez F. Sanmartín M. Riguera R. Eur. J. Med. Chem. 2003, 38: 265

<A NAME="RT53410SS-8">8</A> Chill L. Aknin M. Kashman Y. Org. Lett. 2003, 5: 2433

<A NAME="RT53410SS-9A">9a</A> Pettit GR. Tan R. Xu J. Ichihara Y. Williams MD. Boyd MR. J. Nat. Prod. 1998, 61: 955

<A NAME="RT53410SS-9B">9b</A> Immamura N. Nishijima M. Takadera T. Adachi K. Sakai M. Sano H. J. Antibiot. 1997, 50: 8

<A NAME="RT53410SS-10A">10a</A> Baker DC. Hand ES. Plowman J. Rampal JB. Safavy A. Haugwitz RD. Narayanan VL. Anti-Cancer Drug Des. 1987, 2: 297

<A NAME="RT53410SS-10B">10b</A> For a recent review, see: Pawar VG. De Borggraeve WH. Synthesis 2006, 2799

<A NAME="RT53410SS-11">11</A> Burns CJ, Wil ks AF, and Bu X. inventors; WO 2005,054,230. For a recent example, see: ; Chem. Abstr. 2005, 143, 60004o

<A NAME="RT53410SS-12A">12a</A> Abboto A. Bradamante S. Facchetti A. Pagani GA. J. Org. Chem. 2002, 67: 5753

<A NAME="RT53410SS-12B">12b</A> Wang S. Coord. Chem. Rev. 2001, 215: 79

<A NAME="RT53410SS-12C">12c</A> Balzani V. Juris A. Venturi M. Campagna S. Serroni S. Chem. Rev. 1996, 96: 759

<A NAME="RT53410SS-12D">12d</A> Di Bella S. Chem. Soc. Rev. 2001, 30: 355

<A NAME="RT53410SS-13A">13a</A> Schubert US. Hofmeier H. Newkome GR. Modern Terpyridine Chemistry Wiley-VCH; Weinheim: 2006.

<A NAME="RT53410SS-13B">13b</A> Chelucci G. Thummel RP. Chem. Rev. 2002, 102: 3129

<A NAME="RT53410SS-13C">13c</A> Fache F. Schulz E. Thommasino ML. Lemaire M. Chem. Rev. 2000, 100: 2159

<A NAME="RT53410SS-14">14</A> Garas AMS. Vagg RS. J. Heterocycl. Chem. 2000, 37: 151 ; and references cited therein

<A NAME="RT53410SS-15A">15a</A> Encyclopedia of Supramolecular Chemistry Atwood JL. Steed JW. Marcel Dekker; New York: 2004.

<A NAME="RT53410SS-15B">15b</A> Steed JW. Atwood JL. Supramolecular Chemistry John Wiley & Sons; New York: 2000.

<A NAME="RT53410SS-15C">15c</A> Lehn J.-M. Supramolecular Chemistry: Concepts and Prospectives VCH; Weinheim: 1995.

<A NAME="RT53410SS-15D">15d</A> Steel PJ. Acc. Chem. Res. 2005, 38: 243

<A NAME="RT53410SS-16A">16a</A> Blanco G. Fernández-Mato A. Quintela JM. Peinador C. Synthesis 2009, 438

<A NAME="RT53410SS-16B">16b</A> Blanco G. Fernández-Mato A. Quintela JM. Peinador C. Tetrahedron 2008, 64: 11136

<A NAME="RT53410SS-16C">16c</A> Fernández-Mato A. Blanco G. Quintela JM. Peinador C. Tetrahedron 2008, 64: 3446

<A NAME="RT53410SS-16D">16d</A> Blanco G. Quintela JM. Peinador C. Synthesis 2007, 1397

<A NAME="RT53410SS-16E">16e</A> Blanco G. Quintela JM. Peinador C. Tetrahedron 2007, 63: 2034

<A NAME="RT53410SS-16F">16f</A> Blanco G. Seguí N. Quintela JM. Peinador C. Chas M. Toba R. Tetrahedron 2006, 62: 11124

<A NAME="RT53410SS-16G">16g</A> Blanco G. Quintela JM. Peinador C. J. Heterocycl. Chem. 2006, 43: 1051

<A NAME="RT53410SS-17">17</A> Johnston DBR. inventors; US 4,442,095.

<A NAME="RT53410SS-18">18</A> Schneller SW. Clough FW. J. Heterocycl. Chem. 1975, 12: 513

<A NAME="RT53410SS-19">19</A> For a review see: Janousek Z. Viehe HG. In Iminium Salts in Organic Chemistry, Advances in Organic Chemistry: Chemistry of Dichloromethyleniminium Salts (Phosgeniminium Salts) Vol. 9: Böhme H. Viehe HG. John Wiley & Sons; New York: 1976. p.343

<A NAME="RT53410SS-20A">20a</A> Peinador C. Quintela JM. Moreira MJ. Tetrahedron 1997, 53: 8269

<A NAME="RT53410SS-20B">20b</A> Kokel B. Menichi G. Hobar-Habart M. Tetrahedron Lett. 1984, 25: 1557

<A NAME="RT53410SS-21">21</A> Guillot N. Viehe HG. Tinault B. DeClerq JP. Tetrahedron 1990, 46: 3897

<A NAME="RT53410SS-22">22</A> Bemis GW. Murcko MA. J. Med. Chem. 1996, 39: 2887

<A NAME="RT53410SS-23A">23a</A> Quintela JM. Peinador C. Veiga MC. Botana LM. Alfonso A. Riguera R. Eur. J. Med. Chem. 1998, 33: 887

<A NAME="RT53410SS-23B">23b</A> Beck JR. Yahner JA. J. Org. Chem. 1976, 41: 1733

<A NAME="RT53410SS-24A">24a</A> Hotze ACG. Bacac M. Velders AH. Jansen BAJ. Kooijman H. Spek AL. Haasnoot JG. Reedijk J.
J. Med. Chem. 2003, 46: 1743

<A NAME="RT53410SS-24B">24b</A> Dimmock JR. Vashishtha SC. Quali JW. Pugazhenthi U. Zimple Z. Sudom AM. Allen TM. Kao GY. Balzarini J. DeClercq E. J. Med. Chem. 1999, 42: 4012

<A NAME="RT53410SS-24C">24c</A> Buckley RG. Elsome AM. Fricker SP. Henderson GR. Theobald BRC. Parish RV. Howe BP. Kelland LR. J. Med. Chem. 1996, 39: 5208