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Synthesis 2006(20): 3453-3461  
DOI: 10.1055/s-2006-950210
PAPER
© Georg Thieme Verlag Stuttgart · New York

Facile Synthesis of 3-Carbamoyl-1,2,4-Oxadiazoles

Mina Tamura, Yumiko Ise, Yoshikazu Okajima, Nagatoshi Nishiwaki*, Masahiro Ariga*
Department of Chemistry, Osaka Kyoiku University, Asahigaoka 4-698-1, Kashiwara, Osaka 582-8582, Japan
Fax: +81(72)9783399; e-Mail: nishi@cc.osaka-kyoiku.ac.jp;
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Publication History

Received 19 May 2006
Publication Date:
21 August 2006 (online)

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Abstract

A range of 1,2,4-oxadiazoles, having a carbamoyl group at the 3-position, were synthesized from 2-methyl-4-nitroisoxazolin-5(2H)-one via three steps. Ammonolysis of this nitroisoxazol­one afforded 2-amino-2-hydroxyimino-N-methylacetamide in excellent yield. O-Acylation of this key amidoxime, followed by ring closure, proceeded smoothly to give 3-carbamoyl-1,2,4-oxadiazoles having a substituent at the 5-position which could be easily modified by changing the O-acylating agent. Since each step requires only simple manipulations, the synthetic utility of this procedure is concluded to be high.

Key words

O-acylation - 3-carbamoyl-1,2,4-oxadiazoles - heterocycles - nitroisoxazolone - ring closure

    References

  • 1 Clapp LB. In Advances in Heterocyclic Chemistry   Vol. 20:  Katritzky AR. Academic Press; New York: 1976.  p.66-116  
    Google Scholar
  • 2 Orlek BS. Blaney FE. Brown F. Clark MSG. Hadley MS. Hatcher J. Riley GJ. Rosenberg HE. Wadsworth HJ. Wymann P. J. Med. Chem.  1991,  34:  2726 
    CrossrefPubMedGoogle Scholar
  • 3 Feng DD. Biftu T. Candelore MR. Cascieri MA. Colwell LF. Deng L. Feeney WP. Forrest MJ. Hom GJ. MacIntyre E. Miller RR. Stearns RA. Strader CD. Tota L. Wyvratt MJ. Fisher MH. Weber AE. Bioorg. Med. Chem. Lett.  2000,  10:  1427 
    CrossrefGoogle Scholar
  • 4 Carroll FI. Gray JL. Ablaham P. Kuzemko MA. Lewin AH. Boja JW. Kuhar MJ. J. Med. Chem.  1993,  36:  2886 
    CrossrefGoogle Scholar
  • 5 Diana GD. Volkots DL. Nitzs TJ. Bailey TR. Long MA. Vescio N. Aldous S. Pevear DC. Dutko FJ. J. Med. Chem.  1994,  37:  2421 
    CrossrefGoogle Scholar
  • 6 Ankersen M. Peschke B. Hansen BS. Hansen TK. Bioorg. Med. Chem. Lett.  1997,  7:  1293 
    CrossrefGoogle Scholar
  • 7 Chen C. Senanayake CH. Bill TJ. Larsen RD. Verhoeven VR. Reider PJ. J. Org. Chem.  1994,  59:  3738 
    CrossrefGoogle Scholar
  • 8 Zhang HZ. Kasibhatla S. Kuemmerle J. Kemnitzer W. Ollis-Mason K. Qiu L. Crogan-Grundy C. Tseng B. Drewe J. Cai SX. J. Med. Chem.  2005,  48:  5215 
    CrossrefGoogle Scholar
  • 9 Clapp LB. In Comprehensive Heterocyclic Chemistry   Vol. 6:  Katritzky AR. Peragamon Press; Oxford: 1984.  p.365-391  
    Google Scholar
  • For publications on the preparation of functionalized oxadiazoles, see:
  • 10a Pasinszki T. Westwood NPC. J. Chem. Soc., Chem. Commun.  1995,  1901 
    CrossrefGoogle Scholar
  • 10b Basel Y. Hassner A. Synthesis  1997,  309 
    CrossrefGoogle Scholar
  • 10c Easton CJ. Hughes CMM. Savage GP. Simpson GW. In Advances in Heterocyclic Chemistry   Vol. 60:  Katritzky AR. Academic Press; New York: 1994.  p.261-327  
    CrossrefGoogle Scholar
  • 10d Cosimelli B. Guernelli S. Spinell D. Buscemi S. Frenna V. Macaluso G. J. Org. Chem.  2001,  66:  6124 
    CrossrefGoogle Scholar
  • 10e Hamzé A. Hernandez JF. Fulcrand P. Martinez J. J. Org. Chem.  2003,  68:  7316 
    CrossrefGoogle Scholar
  • 10f Pace A. Pibiri I. Buscemi S. Vivona N. Malpezzi L. J. Org. Chem.  2004,  69:  4108 
    CrossrefGoogle Scholar
  • 10g Kmeti M. Stanovnik B. J. Heterocycl. Chem.  1997,  34:  1705 
    CrossrefGoogle Scholar
  • 10h Buscemi S. Pace A. Piccionello AP. Macaluso G. Vivona N. Spinelli D. Giorgi G. J. Org. Chem.  2005,  70:  3288 
    CrossrefGoogle Scholar
  • 11a Saunders J. Cassidy M. Freedman SB. Harley EA. Iversen LL. Kneen C. MacLeod AM. Merchant KJ. Roger JS. Baker R. J. Med. Chem.  1990,  33:  1128 
    CrossrefGoogle Scholar
  • 11b Bailey S, Billotte S, Derrick AM, Fish PV, James K, and Thomson NM. inventors; PCT Int. Appl. WO  01047901.  (Pfizer Limited) ; Chem. Abstr. 2001, 135, 92633
    Crossref
  • 12 Yarovenko VN. Kasarev SA. Zavarzin IV. Krayushkin MM. Russ. Chem. Bull.  2002,  51:  1857 
    CrossrefGoogle Scholar
  • 13a Nishiwaki N. Nakanishi M. Hida T. Miwa Y. Tamura M. Hori K. Tohda Y. Ariga M. J. Org. Chem.  2001,  66:  7535 
    CrossrefGoogle Scholar
  • 13b Nishiwaki N. Uehara T. Asaka N. Tohda Y. Ariga M. Kanemasa S. Tetrahedron Lett.  1998,  39:  4851 
    CrossrefGoogle Scholar
  • 14 Nishiwaki N. Okajima Y. Tamura M. Asaka N. Hori K. Tohda Y. Ariga M. Heterocycles  2003,  60:  303 
    CrossrefGoogle Scholar
  • 15 Gangloff AR. Litvak J. Shelton EJ. Sperandio D. Wang VR. Rice KD. Tetrahedron Lett.  2001,  42:  1441 
    CrossrefGoogle Scholar
  • 16 Adelfinskaya A. Nashine VC. Bergstrom DE. Davisson VJ. J. Am. Chem. Soc.  2005,  127:  16000 
    CrossrefGoogle Scholar
  • 17 Nishiwaki N. Takada Y. Inoue Y. Tohda Y. Ariga M. J. Heterocycl. Chem.  1995,  32:  473 
    CrossrefGoogle Scholar