Download PDF
Synlett 2002(10): 1718-1720
DOI: 10.1055/s-2002-34246
LETTER
© Georg Thieme Verlag Stuttgart · New York

Microwave-assisted Synthesis of 5-Deaza-5,8-dihydropterins

Mark C. Bagley*, Nivedita Singh
Department of Chemistry, Cardiff University, PO Box 912, Cardiff, CF10 3TB, UK
Fax: +44(29)20874030; e-Mail: bagleymc@cf.ac.uk;
Further Information

Publication History

Received 29 July 2002
Publication Date:
23 September 2002 (online)

    Permissions and Reprints All articles of this category

Abstract

Three-component cyclocondensation of 2,6-diaminopyrimidin-4-one, 1,3-dicarbonyl compounds or benzoylacetonitrile and aromatic or aliphatic aldehydes in the presence or absence of zinc(II) bromide proceeds under microwave-assisted conditions to give 5-deaza-5,8-dihydropterins in good yield and with total control of regiochemistry.

Key words

dihydropyridopyrimidines - three-component cyclocondensations - microwave synthesis - heterocycles - Lewis acids

    References

  • 1a Hopkins FG. Nature (London)  1889,  40:  335 
    Google Scholar
  • 1b Hopkins FG. Nature (London)  1891,  45:  197 
    Google Scholar
  • 1c Hopkins FG. Nature (London)  1892,  45:  581 
    Google Scholar
  • 2 Mitchell HK. Snell EE. Williams RJ. J. Am. Chem. Soc.  1941,  63:  2284 
    Google Scholar
  • 3 Scott JM. Weir DG. Kirke P. In Folate and Neural Tube defects. Folate in Health and Disease   Chap. 12:  Bailey L. B., Marcel Dekker; New York: 1994.  p.329 
    Google Scholar
  • 4a Taylor EC. Palmer DC. George TJ. Fletcher SR. Tseng CP. Harrington PJ. Beardsley GP. J. Org. Chem.  1983,  48:  4852 
    CrossrefGoogle Scholar
  • 4b DeGraw JI. Christie PH. Colwell WT. Sirotnak FM. J. Med. Chem.  1992,  35:  320 
    CrossrefGoogle Scholar
  • 4c Borrell JI. Teixidó J. Matallana JL. Martínez-Teipel B. Colominas C. Costa M. Balcells M. Schuler E. Castillo MJ. J. Med. Chem.  2001,  44:  2366 
    CrossrefGoogle Scholar
  • 5 Grivsky EM. Lee S. Sigel CW. Duch DS. Nichol CA. J. Med. Chem.  1980,  23:  327 
    CrossrefPubMedGoogle Scholar
  • 6a Matsumoto J. Minami S. J. Med. Chem.  1975,  18:  74 
    Google Scholar
  • 6b Suzuki N. Chem. Pharm. Bull.  1980,  28:  761 
    Google Scholar
  • 6c Oakes V. Rydon HN. J. Chem. Soc.  1956,  4433 
    Google Scholar
  • 6d DeGraw JI. Kisliuk RL. Gaumont Y. Baugh CM. J. Med. Chem.  1974,  17:  470 
    Google Scholar
  • 6e Zakharov AV. Gavrilov MY. Novoselova GN. Vakhrin MI. Konshin ME. Khim-Farm. Zh.  1996,  30:  39 
    Google Scholar
  • 7 Deyanov AB. Niyazov RK. Nazmetdinov FY. Syropyatov BY. Kolla VE. Konshin ME. Khim-Farm. Zh.  1991,  25:  26 
    Google Scholar
  • 8 Heckler RE, and Jourdan GP. inventors; Eur. Patent 414  386.  ; Chem. Abstr. 1991, 115, 71630
  • 9 Bagley MC. Hughes DD. Lloyd R. Powers VEC. Tetrahedron Lett.  2001,  42:  6585 
    CrossrefGoogle Scholar
  • 10 Bagley MC. Dale JW. Hughes DD. Ohnesorge M. Phillips NG. Bower J. Synlett  2001,  1523 
    Article in Thieme ConnectGoogle Scholar
  • 11 Bagley MC. Singh N. Chem. Commun.  2001,  2438 
    CrossrefGoogle Scholar
  • 12 Quiroga J. Cisneros C. Insuasty B. Abonía R. Nogueras M. Sánchez A. Tetrahedron Lett.  2001,  42:  5625 
    CrossrefGoogle Scholar
13

In a typical experimental procedure, a mixture of 1,3-diaminopyrimidin-4-one 1 (0.20 g, 1.6 mmol), benzaldehyde (0.34 g, 3.2 mmol), ethyl acetoacetate (0.41 g, 3.2 mmol) and zinc(II) bromide (0.072 g, 0.32 mmol) in DMSO (7 mL) was irradiated for 20 min in a self-tunable CEM microwave synthesizer at 160 °C (initial power 30 W) and then allowed to cool. Water (25 mL) was added and the solution was left to stand for 5-6 h. The precipitated solid was filtered and washed with ethyl acetate to give 5-deaza-5-dihydropterin (3a) (0.38 g, 80%) as a pale yellow solid, mp 179-180 °C (Found: MH+, 327.1454. C17H18N4O3 requires MH, 327.1457); IR (KBr)/cm-1: 3317, 3206, 2936, 1660, 1599, 1515, 1455, 1367, 1285, 1224, 1106, 1024; 1H NMR (DMSO-d 6; 400 MHz) δ (ppm) 10.34 (1 H, 3, 3-H), 9.06 (1 H, s, 8-H), 7.24-7.00 (5 H, m, PhH), 6.27 (2 H, s, NH2), 4.82 (1 H, s, 5-H), 3.94 (2 H, q, J = 7.0 Hz, CH2), 2.31 (3 H, s,
7-Me), 1.10 (3 H, t, J = 7.0 Hz, Me); 13C NMR (DMSO-d 6; 100 MHz) δ (ppm) 167.2 (C), 161.8 (C), 154.4 (C), 154.3 (C), 148.5 (C), 147.5 (C), 128.0 (CH), 127.6 (CH), 125.9 (CH), 101.5 (C), 91.4 (C), 59.2 (CH), 36.8 (CH2), 18.8 (Me), 14.5 (Me); m/z (APcI) 327 (MH+, 100%), 79 (67).