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Synthesis 2012(1): 57-62  
DOI: 10.1055/s-0031-1289587
PAPER
© Georg Thieme Verlag Stuttgart ˙ New York

A Practical, Laboratory-Scale Synthesis of Perampanel

Charles J. McElhinny Jr., F. I. Carroll, Anita H. Lewin*
Research Triangle Institute, 3040 Cornwallis Road, Research Triangle Park, NC 27709, USA
Fax: +1(919)5418868; e-Mail: ahl@rti.org;
Further Information

Publication History

Received 27 September 2011
Publication Date:
04 November 2011 (online)

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Abstract

The orally active, noncompetitive, selective AMPA receptor antagonist Perampanel, 2-[1′,6′-dihydro-6′-oxo-1-phenyl-(2′,3′-bipyridin)-5′-yl]benzonitrile, has been prepared from readily available, relatively inexpensive starting materials. The synthesis was carried out on a laboratory scale with no specialized equipment, and involved only two chromatographic purifications.

Key words

AMPA antagonist - Suzuki coupling - palladium content - Stille coupling - trace-metal contamination

    References

  • 1 Hanada T. Hashizume Y. Tokuhara N. Takenaka O. Kohmura N. Ogasawara A. Hatakeyama S. Ohgoh M. Ueno M. Nishizawa Y. Epilepsia  2011,  52:  1331 
    Search in Google Scholar
  • 2 Arimoto I, Nagato S, Sugaya Y, Urawa Y, Ito K, Naka H, Omae T, Kayano A, and Nishiura K. inventors; US Patent Application  2007/0142640 A1.  (Eisai R & D Management Co. Ltd.) ; Chem. Abstr. 2007, 147, 72649
  • 3 Nagato S, Ueno K, Kawano K, Norimine Y, Ito K, Hanada T, Ueno M, Amino H, Ogo M, Hatakeyama S, Urawa K, Naka H, Groom A, Rivers L, and Smith T. inventors; EP 1300396  A1.  (Eisai Co., Ltd.) ; Chem. Abstr. 2001, 136, 53682
  • 4 Smith T. inventors; Patent WO  2003/047577 A2.  (Eisai Co., Ltd.) ; Chem. Abstr. 2003, 139, 36439
  • 5 Dumas J, Riedl B, Khire U, Sibley RN, Hatoum-Mokdad H, Monahan M.-K, Gunn DE, Lowinger TB, Scott WJ, Smith RA, and Wood JE. inventors; (Bayer Corporation) US Patent Application  2002/0065296.  ; Chem. Abstr. 2002, 137, 6098
  • 6 Miller S, Osterhout M, Dumas J, Khire U, Lowinger TB, Scott WJ, Smith RA, Wood JE, Gunn DE, Hatoum-Mokdad H, Rodriguez M, Sibley R, Wang M, Turner T, and Brennan C. inventors; (Bayer Corporation) US Patent Application  2004/0102636.  ; Chem. Abstr. 2004, 140, 423477
  • 7 Miller S, Osterhout M, Dumas J, Khire U, Lowinger TB, Riedl B, Scott W, Smith R, Wood JE, Gunn D, Hatoum-Mokdad H, Rodriguez MA, Sibley R, Wang M, Turner TI, and Brennan C. inventors; (Bayer Pharmaceuticals Corp.) EP  1042305.  ; Chem. Abstr. 1999, 131, 58659
  • 8 Denton TT. Zhang X. Cashman JR. J. Med. Chem.  2005,  48:  224 
    Search in Google Scholar
  • 9 Spearing PK, Lambert MH, Ray J, Laudeman CP, Szewczyk JR, and Banker P. inventors; (SmithKlineBeecham) Patent WO  2008028118.  ; Chem. Abstr. 2008, 148, 331538
  • 10 Thompson AE. Hughes G. Batsanov AS. Bryce MR. Parry PR. Tarbit B. J. Org. Chem.  2005,  70:  388 
    Search in Google Scholar
  • 11 Parry PR. Wang CH. Batasanov AS. Bryce MR. Tarbit B. J. Org. Chem.  2002,  67:  7541 
    Search in Google Scholar
  • 12 Koyakumaru K, Fukunaga Y, and Satake Y. inventors; (Kuraray Co.; Eisai Co., Ltd.) EP 1553086  A1.  ; Chem. Abstr. 2004, 140, 11287
  • 13 Arimoto I, Nagato S, Sugaya Y, Urawa Y, Ito K, Naka H, and Omae T. inventors; (EISAI R & D Management Co., Ltd.) EPt  1764361 A1.  ; Chem. Abstr. 2006, 144, 128855
  • 14 Omae T, and Sugaya Y. inventors; (Eisai R & D Management Co., Ltd.) EP 1970370  A1.  ; Chem. Abstr. 2007, 147, 95555
  • 15 Urawa Y. inventors; (Eisai R & D Management Co., Ltd.) US Patent  2009/0088574 A1.  ; Chem. Abstr. 2007, 147, 95558