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Synthesis 2013; 45(2): 171-173
DOI: 10.1055/s-0032-1317935
short paper
© Georg Thieme Verlag Stuttgart · New York

A Reliable Synthesis of 3-Amino-5-Alkyl and 5-Amino-3-Alkyl Isoxazoles

Leland Johnson
Novartis Institutes for Biomedical Research, Global Discovery Chemistry, 100 Technology Square, Cambridge, MA 02139, USA   Fax: +1(617)8717044   eMail: nello.mainolfi@novartis.com
,
James Powers
Novartis Institutes for Biomedical Research, Global Discovery Chemistry, 100 Technology Square, Cambridge, MA 02139, USA   Fax: +1(617)8717044   eMail: nello.mainolfi@novartis.com
,
Fupeng Ma
Novartis Institutes for Biomedical Research, Global Discovery Chemistry, 100 Technology Square, Cambridge, MA 02139, USA   Fax: +1(617)8717044   eMail: nello.mainolfi@novartis.com
,
Keith Jendza
Novartis Institutes for Biomedical Research, Global Discovery Chemistry, 100 Technology Square, Cambridge, MA 02139, USA   Fax: +1(617)8717044   eMail: nello.mainolfi@novartis.com
,
Bing Wang
Novartis Institutes for Biomedical Research, Global Discovery Chemistry, 100 Technology Square, Cambridge, MA 02139, USA   Fax: +1(617)8717044   eMail: nello.mainolfi@novartis.com
,
Erik Meredith
Novartis Institutes for Biomedical Research, Global Discovery Chemistry, 100 Technology Square, Cambridge, MA 02139, USA   Fax: +1(617)8717044   eMail: nello.mainolfi@novartis.com
,
Nello Mainolfi*
Novartis Institutes for Biomedical Research, Global Discovery Chemistry, 100 Technology Square, Cambridge, MA 02139, USA   Fax: +1(617)8717044   eMail: nello.mainolfi@novartis.com
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Publikationsverlauf

Received: 24. Oktober 2012

Accepted after revision: 29. November 2012

Publikationsdatum:
19. Dezember 2012 (online)

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Abstract

A reliable procedure that can be used to access a wide range of 3-amino-5-alkyl and 5-amino-3-alkyl isoxazoles was developed. Reaction temperature and pH were key factors that determined the regioselectivity of the two reactions.

Key words

heterocycles - regioselectivity - condensation - medicinal chemistry - imines

Supporting Information

    for this article is available online at http://www.thieme-connect.com/ejournals/toc/synthesis.
  • Supporting Information
 

  • References


      • For examples, see:
    • 1a Du W, Jewell JP, Lin LS, Colandrea VJ, Xiao JC, Lao J, Shen C.-P, Bateman TJ, Reddy VB. G, Ha SN, Shah SK, Fong TM, Jeffrey J, Hagmann WK. Bioorg. Med. Chem. Lett. 2009; 19: 5195
      Crossref
    • 1b Chao Q, Sprankle KG, Grotzfeld RM, Lai AG, Carter TA, Velasco AM, Gunawardane RN, Cramer MD, Gardner MF, James J, Zarrinkar PP, Patel HK, Bhagwat SS. J. Med. Chem. 2009; 52: 7808
      Crossref
    • 2a Quilico A. Gazz. Chim. Ital. 1931; 61: 759
    • 2b Iwai I, Nakamura N. Chem. Pharm. Bull. 1966; 14: 1277
      Crossref
    • 2c Haruki E, Hirai Y, Imoto E. Bull. Chem. Soc. Jpn. 1968; 41: 267
      Crossref
    • 2d Klötzer W, Bretscneider H, Fitz E, Reiner R, Bader G. Monatsh. Chem. 1970; 101: 1109
      Crossref
    • 2e Stachel HD. Chem. Ber. 1963; 96: 1088
      Crossref
    • 2f Takase A, Murabayashi A, Sumimoto S. Heterocycles 1991; 32: 1153
      Crossref
    • 2g Elnagdi MH, Elmoghayar MR. H, Hafez EA. A, Alnima HH. J. Org. Chem. 1975; 40: 2604
      Crossref
    • 2h Rowbottom MW, Faraoni R, Chao W, Campbell BT, Lai AG, Setti E, Ezawa M, Sprankle KG, Abraham S, Tran L, Struss B, Gibney M, Armstrong RC, Gunawardane RN, Nepomuceno RR, Valenta I, Hua H, Gardner MF, Cramer MD, Gitnick D, Insko DE, Apuy JL, Jones-Bolin S, Ghose AK, Herbertz T, Ator MA, Dorsey BD, Ruggeri B, Williams M, Bhagwat S, James J, Holladay MW. J. Med. Chem. 2012; 55: 1082
      Crossref
  • 3 Ji N, Meredith E, Liu D, Adams CM, Artman III GD, Jendza KC, Ma F, Mainolfi N, Powers JJ, Zhang C. Tetrahedron Lett. 2010; 51: 6799
    Crossref
  • 4 CAS numbers: 118431-89-3 (2), 29509-06-6 (15), 118431-88-2 (16), 88485-78-3 (17), and 64373-43-9 (19).
  • 5 Takase and co-workers in ref. 2f report the formation, with reasonable yields, of only 5-aminoisoxazole for any group smaller than t-Bu at 100 °C.