Download PDF
Synthesis 2001(10): 1568-1572
DOI: 10.1055/s-2001-16097
PAPER
© Georg Thieme Verlag Stuttgart · New York

Synthesis of Bioactive Heterocycles: Sigmatropic Rearrangements of 1,3-Dimethyl-6-[methyl(4-aryloxybut-2-ynyl)amino]pyrimidine-2,4(1H,3H)-diones

K. C. Majumdar*, T. Bhattacharyya
Department of Chemistry, University of Kalyani, Kalyani 741 235, W.B., India
Fax: +91(033)5828282; e-Mail: kcm@klyuniv.ernet.in;
Further Information

Publication History

Received 13 March 2001
Publication Date:
29 September 2004 (online)

    Permissions and Reprints All articles of this category

Abstract

A number of 1,3-dimethyl-6-[methyl(4-aryloxybut-2-ynyl)amino]pyrimidine-2,4(1H,3H)-diones 4a-i were synthesised in 69 to 80% yields by the reaction of 6-chloro-1,3-dimethyluracil (6-chloro-1,3-dimethylpyrimidine-2,4(1H,3H)-diones) and 1-aryloxy-4-N-methylaminobut-2-yne in refluxing ethanol for 12 hours. The tertiary amines 4a-i were then heated in refluxing 1,2-dichlorobenzene for 17 hours to give 5-[(E)-aryloxymethylidene]-1,3,8-trimethyl-5,6,7,8-tetrahydropyrido[2,3-d]pyrimidine-2,4(1H,3H)-diones 5a-i in 55 to 75% yields.

Key words

aza-Claisen rearrangement - cyclizations - heterocycles - pyrido[2,3-d]pyrimidine-2,4-diones - sigmatropic rearrangement

    References

  • 1a Lunt E. Comprehensive Organic Chemistry   Vol. 4:  Barton DHR. Ollis WD. Pergamon Press; Oxford: 1974.  p.493 
    CrossrefGoogle Scholar
  • 1b Brown JD. Comprehensive Heterocyclic Chemistry   Vol. 3:  Katritzky AR. Rees CW. Pergamon Press; Oxford: 1984.  p.57 
    CrossrefGoogle Scholar
  • 1c Sasaki T. Minamoto K. Suzuki T. Yamashita S. Tetrahedron  1980,  36:  865  and references cited therein
    CrossrefGoogle Scholar
  • 1d Bradshow TK. Hutchison DW. Chem. Soc. Rev.  1977,  6:  43 
    CrossrefGoogle Scholar
  • 2a Marumato R. Farukawa Y. Chem. Pharm. Bull.  1977,  25:  2974 
    Google Scholar
  • 2b Cheng CC. Roth B. Progr. Med. Chem.  1971,  8:  61 
    Google Scholar
  • 2c Jones AS. Swgers JR. Walker RT. Clercq ED. J. Med. Chem.  1988,  31:  268 
    Google Scholar
  • 2d Griengl HH. Wanck E. Schwarz W. Streicher W. Rosenwirth B. Clercq ED. J. Med. Chem.  1987,  30:  1199 
    Google Scholar
  • 2e Clercq ED. Benaerts R. J. Biol. Chem.  1987,  262:  14905 
    Google Scholar
  • 3 Heidelberger C. Pyrimidine and Pyrimidine Antimetabolites in Cancer Medicine   Holland J. F., Frei E. Lea Febiger; Philadelphia: 1984.  p.801 
    Google Scholar
  • 4 Clercq ED. Descamps J. Somer PD. Barr PJ. Jones AS. Walker RT. Proc. Natl. Acad. Sci. USA  1979,  76:  2947 
    Google Scholar
  • 6 Heidelberger C. King DH. Antiviral Agents in Pharmacology and Theraupeutics   Shugar D. Pergamon Press; Oxford: 1979.  6. p.427 
    Google Scholar
  • 7 Mitsuya H. Weinhold KJ. Furman PA. Clair MH. Lehrman SN. Gallo RC. Bolognesi D. Barry DW. Broder S. Proc. Natl. Acad. Sci. USA  1985,  82:  7096 
    CrossrefGoogle Scholar
  • 8 Fischl MA. Richman DD. Grieco MH. Gottlieb MS. Volberdin PA. Laskin OL. Leedom JM. Groopman JE. Mildvan D. Schooley RT. Jackson GG. Durack DT. King D. N. Eng. J. Med.  1987,  317:  185 
    Google Scholar
  • 9 Griengl H. Bodenteich M. Hayden W. Wanek E. Streicher W. Stutz P. Bachmayer H. Ghazzouli I. Rosenwirth B. J. Med. Chem.  1985,  28:  1679 
    Google Scholar
  • 10 Clercq ED. Descamps J. Ogata M. Shigeta S. Antimicrob. Agents Chemother.  1982,  21:  33 
    Google Scholar
  • 11 Clercq ED. Rosenwirth B. Antimicrob. Agents Chemother.  1985,  28:  246 
    Google Scholar
  • 12 Rosenwirth B. Griengl H. Wanek E. Clercq ED. Antiviral Res.  1985,  Suppl.1:  21 
    Google Scholar
  • 13 Macilwain C. Nature  1993,  365:  378 
    Google Scholar
  • 14 Kundu NG. Dasgupta SK. J. Chem. Soc., Perkin Trans. 1  1993,  2657 
    CrossrefGoogle Scholar
  • 15 Otter BA. Saluja SS. Fox JJ. J. Org. Chem.  1972,  37:  2858 
    Google Scholar
  • 16 Chauhan SMS. Kholi TS. Rao KV. Gulati A. Ind. J. Chem.  1990,  29B:  539 
    Google Scholar
  • 17 Miyasaka T. Tanaka H. Baba M. Hayakawa H. Walker RT. Balzarini J. Clercq ED. J. Med. Chem.  1989,  32:  2507 
    CrossrefGoogle Scholar
  • 18 Baba M. Tanaka H. Clercq ED. Pauwels R. Balzarini J. Schols D. Nakashima H. Perno CF. Walker RT. Miyasaka T. Biochem. Biophys. Res. Commun.  1989,  165:  1375 
    CrossrefGoogle Scholar
  • 19 Clercq ED. Medicinal Res. Rev.  1993,  13:  229 
    Google Scholar
  • 20a Gallo RC. Sci. Am.  1986,  255:  78 
    Google Scholar
  • 20b Gallo RC. Sci. Am.  1987,  256:  46 
    Google Scholar
  • 21 Kawahara N. Nakajima T. Itoh T. Ogura H. Chem. Pharm. Bull.  1985,  33:  4740 
    CrossrefGoogle Scholar
  • 22a Majumdar KC. Das U. J. Chem. Res., Synop.  1997,  309 
    Google Scholar
  • 22b Majumdar KC. Das U. J. Chem. Res., Miniprint  1997,  2062 
    Google Scholar
  • 22c Majumdar KC. Das U. Synth. Commun.  1997,  27:  4013 
    Google Scholar
  • 23 Majumdar KC. Das U. Jana NK. J. Org. Chem.  1998,  63:  3550 
    CrossrefGoogle Scholar
  • 24 Itoh T. Imini T. Ogura H. Kawahara N. Nakajima T. Watanabe KA. Chem. Pharm. Bull.  1985,  33:  1379 
    Google Scholar
  • 25 Marcinkiewcz S. Green J. Mamalis P. Tetrahedron  1961,  14:  208 
    CrossrefGoogle Scholar
  • 26 Claisen L. Ber. Dtsch. Chem. Ges.  1912,  45:  3157 
    CrossrefGoogle Scholar
  • 27a Zsindely J. Schmidt H. Helv. Chim. Acta.  1968,  51:  1510 
    Google Scholar
  • 27b Majumdar KC. Thyagarajan BS. Balasubramanian KK. J. Heterocycl. Chem.  1973,  10:  159 
    Google Scholar
  • 28 Majumdar KC. Das U. J. Org. Chem.  1998,  63:  9997 
    CrossrefGoogle Scholar
  • 29 Ramakanth S. Narayanan K. Balasubramanian KK. Tetrahedron Lett.  1984,  25:  103 
    CrossrefGoogle Scholar
  • 30 Majumdar KC. Das DP. Jana GH. Khan AT. Ind. J. Chem.  1994,  33B:  120 
    Google Scholar
  • 31 Majumdar KC. Choudhury PK. Synth. Commun.  1994,  23:  1087 
    Google Scholar
  • 32 Majumdar KC. Jana GH. Synthesis  2001,  924 
    Article in Thieme ConnectGoogle Scholar
  • 33 Majumdar KC. Jana NK. Synth. Commun.  2000,  30:  2613 
    Google Scholar
  • 34a Suzuki N. Chem. Pharm. Bull.  1980,  28:  761 
    Google Scholar
  • 34b Grivsky EM. Lee S. Siegel CW. Duck DS. Nichol CA. J. Med. Chem.  1980,  23:  327 
    Google Scholar
  • 34c Kretzschmer E. Pharmazie  1980,  35:  253 
    Google Scholar