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Synlett 2017; 28(10): 1183-1186
DOI: 10.1055/s-0036-1588954
letter
© Georg Thieme Verlag Stuttgart · New York

Efficient Synthesis of 3-Amino-1,5-benzodiazepine-2-one Derivatives

Nobuhiro Obara*
a   Zeria Pharmaceutical Co., Ltd, 2512-1, Numagami, Oshikiri, Kumagaya-city, Saitama 360-0111, Japan
,
Takeshi Watanabe
a   Zeria Pharmaceutical Co., Ltd, 2512-1, Numagami, Oshikiri, Kumagaya-city, Saitama 360-0111, Japan
,
Tomohiro Asakawa
b   School of Pharmaceutical Sciences, University of Shizuoka, 52-1, Yada, Suruga-ku, Shizuoka-city, Shizuoka 422-8526, Japan
c   Tokai University Institute of Innovative Science and Technology, 4-1-1, Kitakaname, Hiratsuka-city, Kanagawa 259-1292, Japan
,
Toshiyuki Kan
b   School of Pharmaceutical Sciences, University of Shizuoka, 52-1, Yada, Suruga-ku, Shizuoka-city, Shizuoka 422-8526, Japan
,
Takao Tanaka
a   Zeria Pharmaceutical Co., Ltd, 2512-1, Numagami, Oshikiri, Kumagaya-city, Saitama 360-0111, Japan
› Author Affiliations
Further Information

Publication History

Received: 22 December 2016

Accepted after revision: 26 January 2017

Publication Date:
23 February 2017 (online)

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Abstract

A convenient method for synthesizing 3-amino-1,5-benzodiazepine-2-one via the Michael addition reaction of o-phenylenediamine with dehydroalanine ester derivatives, followed by cyclization, was developed. This simple method was used to obtain a variety of N-substituted 3-amino-1,5-benzodiazepine-2-ones in one pot with good yields.

Key words

dehydroalanine - o-phenylenediamine - Michael addition reaction - 3-amino-1,5-benzodiazepine-2-one - polarized carbon–carbon double bond

Supporting Information

    Supporting information for this article is available online at http://dx.doi.org/10.1055/s-0036-1588954.
  • Supporting Information
 

  • References and Notes

    • 1a Hoyt SB, London C, Wyvratt MJ, Fisher MH, Cashen DE, Felix JP, Garcia ML, Li X, Lyons KA, MacIntyre DE, Martin WJ, Priest BT, Smith MM, Warren VA, Williams BS, Kaczorowski GJ, Parsons WH. Bioorg. Med. Chem. Lett. 2008; 18: 1963-1963
      CrossrefPubMed
    • 1b Williams BS, Felix JP, Priest BT, Brochu RM, Dai K, Hoyt SB, London C, Tang YS, Duffy JL, Parsons WH, Kaczorowski GJ, Garcia ML. Biochemistry 2007; 46: 14693-14693
      CrossrefPubMed
  • 2 Churcher I, Williams S, Kerrad S, Harrison T, Castro JL, Shearman MS, Lewis HD, Clarke EE, Wrigley JD. J, Beher D, Tang YS, Liu W. J. Med. Chem. 2003; 46: 2275-2275
    CrossrefPubMed
  • 3 Kester RF, Donnell AF, Lou Y, Remiswzewski SW, Lombardo LJ, Chen S, Le NT, Lo J, Moliterni JA, Han X, Hogg JH, Liang W, Michoud C, Rupert KC, Mischke S, Le K, Weisel M, Janson CA, Lukacs CM, Fretland AJ, Hong K, Polonskaia A, Gao L, Li S, Solis DS, Aguilar D, Tardell C, Dvorozniak M, Tannu S, Lee EC, Schutt AD, Goggin B. J. Med. Chem. 2013; 56: 7788-7788
    CrossrefPubMed
  • 4 Lauffer DJ, Mullican MD. Bioorg. Med. Chem. Lett. 2002; 12: 1225-1225
    CrossrefPubMed
  • 5 Kawasaki D, Emori Y, Eta R, Iino Y, Hamano H, Yoshinaga K, Tanaka T, Takei M, Watson SA. Cancer Chemother. Pharmacol. 2008; 61: 883-883
    CrossrefPubMed
    • 6a Chen S, Donnell AF, Kester RF, Le K, Lou Y, Michoud C, Remiszewski S, Rupert KC, Weisel M. WO 2015071393A1, 2015
      PubMed
    • 6b Bandyopadhyay D, Eidam PM, Gough PJ, Harris PA, Jeong JU, Kang J, King BW, Lakdawala SA, Marquis RW. Jr, Leister LK, Rahman A, Ramanjulu JM, Sheon CA, Singhaus RJr, Zhang D. WO 2014125444A1, 2014
      PubMed
    • 6c Donnell AF, Kester RF, Lou Y, Moliterni JA, Remiszewski S. WO 2014044622A1, 2014
      PubMed
    • 6d Asai M, Haketa T, Inamura S, Ishikawa M, Jona H, Kawamoto H, Kurihara H, Shibata J, Shimamura T, Suga T, Watanabe H. WO 2010084979A1, 2010
      PubMed
    • 6e Lauffer DJ, Mullican MD. Bioorg. Med. Chem. Lett. 2002; 12: 1225-1225
      CrossrefPubMed
    • 6f Bemis GW, Golec JM. C, Lauffer DJ, Mullican MD, Murcko MA, Livingston DJ. WO 9535308A1, 1995
      PubMed
    • 7a Hussenether T, Hübner H, Gmeiner P, Troschütz R. Bioorg. Med. Chem. 2004; 12: 2625-2625
      CrossrefPubMed
    • 7b Hirata K, Ogawa N, Shinagawa Y, Kiguchi T, Inoue T, Komeda Y, Yamashita I, Kamiya Y. WO 2007139002A1, 2007
      PubMed
    • 7c Bachman GB, Heisey LV. J. Am. Chem. Soc. 1949; 71: 1985-1985
      Crossref
    • 8a Claremon DA, Liverton N, Selnick HG, Smith GR. WO 9640653A1, 1996
      PubMed
    • 8b Claremon DA, Freidinger RM, Liverton N, Selnick HG, Smith GR. WO 9640656A1, 1996
      PubMed
    • 8c Carmel JS, Stanton JL. US 4477464, 1984
      PubMed
  • 9 Berry JM, Doyle PM, Young DW. Tetrahedron Lett. 2002; 43: 8963-8963
    Crossref
  • 10 Regueiro-Ren A, Ueda Y. J. Org. Chem. 2002; 67: 8699-8699
    CrossrefPubMed
  • 11 Reaction of 1 with 2l A mixture of 1 (500 mg, 4.62 mmol) and N-Ac-dehydroalanine 1,1,1,3,3,3-hexafluoroisopropyl ester (2l; 1.29 g, 4.62 mmol) in toluene (5 mL) was stirred at reflux for 2 h. The mixture was cooled to ambient temperature, and EtOAc (5 mL) was added. The precipitate was filtered and washed with an EtOAc–toluene mixture (1:1) to give 3a (768 mg, 3.50 mmol, 76% yield) as a pale yellow solid. Spectral Data for 3a 1H NMR (400 MHz, DMSO-d 6): δ = 9.77 (1 H, s), 8.10 (1 H, d, J = 7.7 Hz), 6.87–6.95 (2 H, m), 6.83 (1 H, d, J = 7.7 Hz), 6.71 (1 H, td, J = 7.7, 1.3 Hz), 5.70 (1 H, d, J = 6.2 Hz), 4.46 (1 H, ddd, J = 10.8, 7.7, 4.6 Hz), 3.48 (1 H, ddd, J = 10.8, 6.2, 4.6 Hz) 3.28 (1 H, td, J = 10.8, 0.7 Hz), 1.87 (3 H, s) ppm. 13C NMR (100 MHz, DMSO-d 6): δ = 170.89, 168.91, 139.76, 125.86, 125.03, 122.51, 119.29, 118.97, 51.59, 50.43, 22.42 ppm. FTIR (KBr): 3362, 3225, 1671, 1634, 1535, 1510, 1445, 1333, 737 cm–1. ESI-HRMS: m/z calcd for C11H14N3O2 [M + H]+: 220.1081; found: 220.1079.
  • 12 Ohfune Y, Kan T, Nakajima T. Tetrahedron 1998; 54: 5207-5207
    Crossref