Download PDF
Synthesis 2001(11): 1711-1715
DOI: 10.1055/s-2001-16768
PAPER
© Georg Thieme Verlag Stuttgart · New York

O-Pyrazolylpropynyl-Hydroxylamines as Versatile Intermediates in the Synthesis of Compounds of Pharmacological Interest

María Isabel Rodríguez-Franco*, Isabel Dorronsoro, Ana Martínez
Instituto de Química Médica (C.S.I.C.), Juan de la Cierva 3, 28006 Madrid, Spain
Fax: +34(91)5644853; e-Mail: IsabelRguez@iqm.csic.es;
Further Information

Publication History

Received 11 May 2001
Publication Date:
12 August 2004 (online)

    Permissions and Reprints All articles of this category

Abstract

Through an optimised Pd/Cu-catalysed cross-coupling reaction of 4-iodopyrazoles with 2-propyn-1-ol, followed by Mitsunobu transformation with N-hydroxyphthalimide and subsequent hydrazinolysis, O-[(pyrazol-4-yl)-prop-2-ynyl]-hydroxylamines were obtained in good yields. Their usefulness as intermediates in the synthesis of pharmaceuticals is exemplified by the first reported intramolecular cyclization of O-(2-propynyl)-hydroxylamines to yield 4,5-dihydro-isoxazoles.

Key words

O-pyrazolylpropynyl-hydroxylamines - 3-pyrazolyl-4,5-dihydro-isoxazoles - cross-coupling - Mitsunobu reaction - intramolecular cyclisation

    References

  • 2 Tecle H. Barrett SD. Lauffer DJ. Augelli-Szafran C. Brann MR. Callahan MJ. Caprathe BW. Davis RE. Doyle PD. Eubanks D. Lipiniski W. Mirzadegan T. Moos WH. Moreland DW. Nelson CB. Pavia MR. Raby C. Schwarz RD. Spencer CJ. Thomas AJ. Jaén JC. J. Med. Chem.  1998,  41:  2524 
    CrossrefGoogle Scholar
  • 3 Inglesi M. Nicola M. Magnetti S. Farmaco  1990,  45:  1327 
    Google Scholar
  • 4a Peixoto C. Laurin P. Klich M. Dupuis-Hamelin C. Mauvais P. Lassaigne P. Bonnefoy A. Musicki B. Tetrahedron Lett.  2000,  41:  1741 
    CrossrefGoogle Scholar
  • 4b Tsubouchi H. Tsuji K. Yasumura K. Ishikawa H. Chem. Pharm. Bull.  1994,  42:  2084 
    CrossrefGoogle Scholar
  • 4c Ternansky RJ. Draheim SE. Pike AJ. Counter FT. Eudaly JA. Kasher JS. J. Med. Chem.  1993,  36:  3224 
    CrossrefGoogle Scholar
  • 5 Sawaikar DD. Sinha B. Hebbalkar GD. Sharma RN. Patwardhan SA. Indian J. Chem., Sect. B  1995,  34:  832 
    Google Scholar
  • 6 Kocur J. Mildenberger H. Sachse B. Z. Naturforsch., B.: Chem. Sci.  1982,  37:  902 
    Google Scholar
  • 7a Rodríguez-Franco MI. Dorronsoro I. Martínez A. Pérez C. Badía A. Baños JE. Arch. Pharm., Pharm. Med. Chem.  2000,  333:  118 
    CrossrefGoogle Scholar
  • 7b Rodríguez-Franco MI. Dorronsoro I. Castro A. Martínez A. Tetrahedron  2000,  56:  1739 
    CrossrefGoogle Scholar
  • 8a Rodríguez-Franco MI. San Lorenzo P. Martínez A. Navarro P. Tetrahedron  1999,  55:  2763 
    Google Scholar
  • 8b Rodríguez-Franco MI. Fierros M. Martínez A. Navarro P. Conde S. Bioorg. Med. Chem.  1997,  5:  363 
    Google Scholar
  • 9 Sonogashira K. Tohda Y. Hagihara N. Tetrahedron Lett.  1975,  50:  4467 
    Google Scholar
  • 10 Mitsunobu O. Eguchi M. Bull. Chem. Soc. Jpn.  1971,  44:  3427 
    CrossrefGoogle Scholar
  • 11 Pitts WJ. Wityak J. Smallheer JM. Tobin AE. Jetter JW. Buynitsky JS. Harlow PP. Solomon KA. Corjay MH. Mousa SA. Wexler RR. Jadhav PK. J. Med. Chem.  2000,  43:  27 
    CrossrefGoogle Scholar
  • 12 Rodríguez-Franco MI. Dorronsoro I. Hernández-Higueras AI. Antequera G. Tetrahedron Lett.  2001,  42:  863 
    CrossrefGoogle Scholar
  • 13 Tolf B.-R. Dahlbom R. Theorell H. Åkeson Å. Acta Chem. Scand., Ser. B  1982,  36:  101 
    Google Scholar
  • 14a Tretyakov EV. Knight DW. Vasilevsky S. J. Chem. Soc., Perkin Trans. 1  1999,  3713 
    CrossrefGoogle Scholar
  • 14b Alami M. Ferri F. Linstrumelle G. Tetrahedron Lett.  1993,  34:  6403 
    CrossrefGoogle Scholar
  • 15 Brandsma L. Vasilevsky SF. Verkruijsse HD. Application of Transition Metal Catalysts in Organic Synthesis   Springer-Verlag; Berlin: 1999.  p.179 
    Google Scholar
  • 16 Mitsunobu O. Synthesis  1981,  1 
    Article in Thieme ConnectGoogle Scholar
  • 17 Grochowski E. Jurczak J. Synthesis  1976,  682 
    Article in Thieme ConnectGoogle Scholar
  • 18 Xu R. Sim M.-K. Go M.-L. J. Med. Chem.  1998,  41:  3220 
    CrossrefGoogle Scholar
  • 19 March J. Advanced Organic Chemistry: Reactions, Mechanisms, and Structure   3rd ed.:  John Wiley; New York: 1985.  p.689 
    Google Scholar
  • 20a McGrane PL. Jensen M. Livinghouse T. J. Am. Chem. Soc.  1992,  114:  5459 
    CrossrefGoogle Scholar
  • 20b McGrane PL. Livinghouse T. J. Org. Chem.  1992,  57:  1323 
    CrossrefGoogle Scholar
  • 20c Fukuda Y. Utimoto K. Synthesis  1991,  975 
    CrossrefGoogle Scholar
  • 20d Fukuda Y. Matsubara S. Utimoto K. J. Org. Chem.  1991,  56:  5812 
    CrossrefGoogle Scholar
  • 21 Li Y. Marks TJ. J. Am. Chem. Soc.  1996,  118:  9295 
    CrossrefGoogle Scholar
  • 22a Sheradsky T. Nov E. Segal S. Frank A. J. Chem. Soc., Perkin Trans. 1  1977,  1827 
    CrossrefGoogle Scholar
  • 22b Blatt AH. J. Am. Chem. Soc.  1939,  61:  3494 
    CrossrefGoogle Scholar
  • 23a Pradhan SK. Akamanchi KG. Divakaran PP. Pradhan PM. Heterocycles  1989,  28:  813 
    CrossrefGoogle Scholar
  • 23b Pradhan SK. Akamanchi KG. Divakaran PP. Tetrahedron Lett.  1983,  24:  5017 
    CrossrefGoogle Scholar
  • 24a Olson RE. Sielecki TM. Wityak J. Pinto DJ. Batt DG. Frietze WE. Liu J. Tobin AE. Orwat MJ. Meo SVD. Houghton GC. Lalka GK. Mousa SA. Racanelli AL. Hausner EA. Kapil RP. Rabel SR. Thoolen MJ. Reilly TM. Anderson PS. Wexler RR. J. Med. Chem.  1999,  42:  1178 
    CrossrefGoogle Scholar
  • 24b Quan ML. Ellis CD. Liauw AY. Alexander RS. Knabb RM. Lam G. Wright MR. Wong PC. Wexler RR. J. Med. Chem.  1999,  42:  2760 
    CrossrefGoogle Scholar
  • 25a Kleinman EF. Campbell E. Giordano LA. Cohan VL. Jenkinson TH. Cheng JB. Shirley JT. Pettipher ER. Salter ED. Hibbs TA. DiCapua FM. Bordner J. J. Med. Chem.  1998,  41:  266 
    Google Scholar
  • 25b Khalil MA. Soliman R. Farghaly AM. Bekhit AA. Arch. Pharm.  1994,  327:  27 
    Google Scholar
  • 26a Hara R. Itahana H. Sakamoto K. Hiusamichi H. Nagano N. J. Antibiot.  1996,  49:  1182 
    Google Scholar
  • 26b Burton G. Clarke GJ. Douglas JD. Eglington AJ. Frydrych CH. Hinks JD. Hird NW. Hunt E. Moss SF. Naylor A. Nicholson NH. Pearson MJ. J. Antibiot.  1996,  49:  1266 
    Google Scholar
  • 27 Rodríguez-Franco MI. Dorronsoro I. Martínez A. Castro A. J. Heterocycl. Chem.  2001,  38:  435 
    Google Scholar
  • 28 Morgan GT. Ackerman I. J. Chem. Soc.  1923,  123:  1304 
    Google Scholar
1

This paper comprises a part of Isabel Dorronsoro’s Ph.D. thesis.