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Synlett 2005(5): 0834-0838  
DOI: 10.1055/s-2005-863735
LETTER
© Georg Thieme Verlag Stuttgart · New York

Expedient Syntheses of Sulfonylhydantoins and Two Six-Membered Analogues

Andrew D. Campbell*, Alan M. Birch
AstraZeneca Research and Development, Mereside, Alderley Park, Macclesfield, Cheshire, SK10 4TG, UK
Fax: +44(1625)516667; e-Mail: andrew.campbell2@astrazeneca.com;
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Publikationsverlauf

Received 26 October 2004
Publikationsdatum:
09. März 2005 (online)

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Abstract

A range of α-amino esters can be turned into sulfonyl­hydantoins 2 in a single, atom-economic step using sulfamide and DBU. This procedure obviates the need for a three- or four-step sequence utilised by traditional procedures. Two new six-membered analogues 3 and 4 have also been prepared utilising novel synthetic protocols.

Key words

amino acids - sulfonamides - heterocycles - medicinal chemistry - phosphates

    References

  • 1 Vorreither HK. Ziegler E. Monatsh. Chem.  1965,  96:  216 
    CrossrefGoogle Scholar
  • 2a Kuang R. Epp JS. Ruan S. Chong LS. Venkataraman R. Tu J. He S. Truong TM. Groutas WC. Bioorg. Med. Chem.  2000,  8:  1005 
    CrossrefGoogle Scholar
  • 2b Kuang R. Epp JS. Ruan S. Yu H. Huang P. He S. Tu J. Schechter NM. Turbov J. Froelich CJ. Groutas WC. J. Am. Chem. Soc.  1999,  121:  8128 
    CrossrefGoogle Scholar
  • 3a Albericio F. Garcia J. Michelotti EL. Nicolás E. Tice CM. Tetrahedron Lett.  2000,  41:  3161 
    CrossrefGoogle Scholar
  • 3b Albericio F. Bryman LM. Garcia J. Michelotti EL. Nicolás E. Tice CM. J. Comb. Chem.  2001,  3:  290 
    CrossrefGoogle Scholar
  • 4 Mantegani S. Brambilla E. Caccia C. Chiodini L. Ruggieri D. Lamberti E. Di Salle E. Salvati P. Farmaco  1998,  53:  293 
    CrossrefGoogle Scholar
  • 5 Muller GW. DuBois GE. J. Org. Chem.  1989,  54:  4471 
    Google Scholar
  • 6a Crenshaw RR, and Algieri AA. inventors; U.S. Patent  4,394,508. 
    Crossref
  • 6b Duery L. Reinelt S. Seiler P. Diederich F. Helv. Chim. Acta  1999,  82:  2432 
    CrossrefGoogle Scholar
  • 6c Dewynter G. Aouf N. Regainia Z. Montero J.-L. Tetrahedron  1996,  52:  993 
    CrossrefGoogle Scholar
  • 7a Coppola GM, Davies JW, Jewell CF, Li C.-Y, Wareing JR, Sperbeck DM, Stams TM, Topiol SW, and Vlattas I. inventors; WO  2003/082841.  ; Chem. Abstr. 2003, 139: 307766
  • 7b Saunders JO, Miknis GF, and Blake JF. inventors; WO  2004/062664.  ; Chem. Abstr. 2004, 141, 157120
  • 8 Lee C.-H. Korp JD. Kohn HJ. J. Org. Chem.  1989,  54:  3077 
    CrossrefGoogle Scholar
  • 9 Graf R. Chem. Ber.  1959,  92:  509 
    Google Scholar
  • 10 Lee H.-C. Kohn HJ. J. Org. Chem.  1990,  55:  6098 
    Google Scholar
  • 12 Tan CYK. Weaver DF. Tetrahedron  2002,  58:  7449 ; and references cited therein
    CrossrefGoogle Scholar
  • 13 Morris J. Wishka DG. J. Org. Chem.  1991,  56:  3549 
    CrossrefGoogle Scholar
  • 14 Dolongo S. Bodina RI. Lipina S. Berkova GA. Perekalin VV. J. Org. Chem. USSR  1991,  27:  1951 
    Google Scholar
  • 15 Hawkins JM. Lewis TA. Raw AS. Tetrahedron Lett.  1990,  31:  981 
    CrossrefGoogle Scholar
  • 16 Chatterjee AK. Choi T.-L. Grubbs RH. Synlett  2001,  1034 
    Artikel in Thieme ConnectGoogle Scholar
11

Sulfamide (159 mg, 1.65 mmol) was added to methyl N-(2-methoxybenzyl)glycinate (345 mg, 1.65 mmol) followed by addition of DBU (0.25 mL, 1.65 mmol) in a 10 mL pyrex tube under an argon stream. The reaction was then heated to 160 °C at which point the reaction became homogeneous and bubbling was observed. After 15 min, the reaction was cooled to r.t. and diluted with 1 M NaOH (40 mL) and Et2O (20 mL) and shaken until all the gum dissolved. The aqueous layer was separated, acidified with 6 M HCl until pH 1 and then extracted with EtOAc (2 × 20 mL). The combined EtOAc layers were dried (MgSO4), filtered and evaporated to form a beige solid. Trituration with Et2O-hexanes (1:5, 5 mL) followed by filtration afforded the sulfonylhydantoin product (Table [1] entry 4, 190 mg, 0.742 mmol, 45%) as an off-white solid. 1H NMR (300 MHz, DMSO): δ = 3.80 (s, 3 H), 4.00 (s, 2 H), 4.24 (s, 2 H), 6.93 (t, J = 7.5 Hz, 1 H), 7.01 (d, J = 8.0 Hz, 1 H), 7.29-7.37 (m, 2 H), 8.60 (br s, 1 H). 13C NMR (75 MHz, DMSO): δ = 45.1, 55.3, 55.8, 111.3, 120.7, 123.7, 129.7, 129.9, 157.5, 168.6. HRMS (TOF MS EI+): m/z calcd for C10H12N2O4S: 256.0518; found: 256.0521.