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Synlett 2010(11): 1682-1684  
DOI: 10.1055/s-0029-1220126
LETTER
© Georg Thieme Verlag Stuttgart ˙ New York

Reactions of Heterocyclic Ketene Aminals with 2-[3-Oxoisobenzofuran-1(3H)-ylidene]malononitrile: Synthesis of Novel Polyfunctionalized 1,4-Dihydropyridine-Fused 1,3-Diazaheterocycles

Wen-Yuan Xua,b, Yue-Mei Jiab, Jing-Kui Yang*a, Zhi-Tang Huang*b, Chu-Yi Yu*b
a College of Chemistry and Chemical Engineering, Graduate University of Chinese Academy of Sciences, Beijing 100049, P. R. of China
b Beijing National Laboratory for Molecular Science (BNLMS), CAS Key Laboratory of Molecular Recognition and Function, Institute of Chemistry, Chinese Academy of Sciences, Beijing 100190, P. R. of China
Fax: +86(10)82616433; e-Mail: yucy@iccas.ac.cn;
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Received 8 April 2010
Publikationsdatum:
01. Juni 2010 (online)

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Abstract

An efficient method has been developed for the synthesis of a novel kind of polyfunctionalized 1,4-dihydropyridine-fused 1,3-diazaheterocycles via the reactions of heterocyclic ketene aminals (HKAs) with 2-[3-oxoisobenzofuran-1(3H)-ylidene]malono­nitrile.

Key words

heterocyclic ketene aminals - polyfunctionalized - 1,4-dihydropyridine-fused 1,3-diazaheterocycles - synthesis

    References and Notes

  • 1a Huang Z.-T. Wamhoff H. Chem. Ber.  1984,  117:  622 
    Suche in Google Scholar
  • 1b Basheer A. Rappoport Z. J. Org. Chem.  2006,  71:  9743 
    Suche in Google Scholar
  • For reviews, see:
  • 1c Huang Z.-T. Wang M.-X. Heterocycles  1994,  37:  1233 
    Suche in Google Scholar
  • 1d Wang M.-X. Huang Z.-T. Prog. Nat. Sci.  2002,  12:  249 
    Suche in Google Scholar
  • 2a Destro R. Cosentino U. Moro G. Ortoleva E. Pilati T. J. Mol. Struct.  1989,  212:  97 
    Suche in Google Scholar
  • 2b Anderson MW. Begley MJ. Jones RCF. J. Chem. Soc., Perkin Trans. 1  1984,  2599 
  • 2c Jones RCF. Patel P. Hirst SC. Smallridge MJ. Tetrahedron  1998,  54:  6191 
    Suche in Google Scholar
  • 2d Baum K. Bigelow SS. Nanyen NV. Archibald TG. Gilardi R. Flippen-Anderson JL. Georeg C. J. Org. Chem.  1992,  57:  235 
    Suche in Google Scholar
  • For recent examples, see:
  • 3a Zeng C.-C. Liu F.-J. Ping D.-W. Hu L.-M. Cai Y.-L. Zhong R.-G. J. Org. Chem.  2009,  74:  6386 
    Suche in Google Scholar
  • 3b Yu C.-Y. Yang P.-H. Zhao M.-X. Huang Z.-T. Synlett  2006,  1835 
  • 3c Ram VJ. Goel A. Sarkhel S. Maulik PR. Bioorg. Med. Chem.  2002,  10:  1275 
    Suche in Google Scholar
  • 4a Wang M.-X. Huang Z.-T. J. Org. Chem.  1995,  60:  2807 
    Suche in Google Scholar
  • 4b Zhao W.-Y. Huang Z.-T. J. Chem. Soc., Perkin Trans. 2  1991,  1967 
  • 5a Huang Z.-T. Wang M.-X. J. Org. Chem.  1992,  57:  184 
    Suche in Google Scholar
  • 5b Yang Q. Li Z.-J. Chen X.-M. Huang Z.-T. Heteroat. Chem.  2002,  13:  242 ; and references therein
    Suche in Google Scholar
  • 6a Liao J.-P. Zhang T. Yu C.-Y. Huang Z.-T. Synlett  2007,  761 
  • 6b Yaqub M. Yu C.-Y. Jia Y.-M. Huang Z.-T. Synlett  2008,  1357 
  • 6c Yan S.-J. Huang C. Sun C.-X. Ni Y.-F. Lin J. J. Comb. Chem.  2010,  12:  91 
    Suche in Google Scholar
  • 6d Pratap R. Sharon A. Maulik PR. Ram VJ. Tetrahedron Lett.  2005,  46:  85 
    Suche in Google Scholar
  • 7a Tomizawa M. Otsuka H. Miyamoto T. Eldefrawi ME. Yamamoto I. J. Pestic. Sci.  1995,  20:  57 
    Suche in Google Scholar
  • 7b Tieman CH, and Kollmeyer WD. inventors; U.S. Patent  3948934. 
  • 7c Shao X.-S. Fu H. Xu X.-Y. Xu X.-L. Liu Z.-W. Li Z. Qian X.-H. J. Agric. Food Chem.  2010,  58:  2696 
    Suche in Google Scholar
  • 8a Abdelhalim MM. El-Saidib MMT. Rabie ST. Elmegeeda GA. Steroids  2007,  72:  459 
    Suche in Google Scholar
  • 8b Kondo H. Taguchi M. Inoue Y. Sakamoto F. Tsukamoto G.
    J. Med. Chem.  1990,  33:  2012 
    Suche in Google Scholar
  • 9a Jordan AD. Vaidya AH. Rosenthal DI. Dubinsky B. Kordik CP. Sanfilippo PJ. Wu WN. Reitz AB. Bioorg. Med. Chem. Lett.  2002,  12:  2381 
    Suche in Google Scholar
  • 9b Maryanoff BE. Nortey SO. McNally JJ. Sanfilippo PJ. McComsey DF. Dubinsky B. Shank RP. Reitz AB. Bioorg. Med. Chem. Lett.  1999,  9:  1547 
    Suche in Google Scholar
  • 9c Maryanoff BE. Ho W. McComsey DF. Reitz AB. Grous PP. Nortey SO. Shank RP. Dubinsky B. Taylor RJ. Gardocki JF. J. Med. Chem.  1995,  38:  16 
    Suche in Google Scholar
  • 10 Suryawanshi SN. Pandey S. . Bhatt BA. Gupta S. Eur. J. Med. Chem.  2007,  42:  511 
    CrossrefSuche in Google Scholar
  • 11 Yan S.-J. Huang C. Zeng X.-H. Huang R. Lin J. Bioorg. Med. Chem. Lett.  2010,  20:  48 
    CrossrefSuche in Google Scholar
  • For reviews, see:
  • 12a Saragi TPI. Spehr T. Siebert A. Fuhrmann-Lieker T. Salbeck J. Chem. Rev.  2007,  107:  1011 
    Suche in Google Scholar
  • 12b Pudzich R. Fuhrmann-Lieker T. Salbeck J. Adv. Polym. Sci.  2006,  199:  83 
    Suche in Google Scholar
  • 13 Xie J.-H. Zhou Q.-L. Acc. Chem. Res.  2008,  41:  581 
    CrossrefSuche in Google Scholar
  • 14 Francke W. Kitching W. Curr. Org. Chem.  2001,  5:  233 
    CrossrefSuche in Google Scholar
  • 15 Haruyama H. Takayama T. Kinoshita T. Kondo M. Nakajima M. Haneishi T. J. Chem. Soc., Perkin Trans. 1  1991,  1637 
    Crossref
  • 16a Kotha S. Chandras Deb A. Lahiri K. Manivannan E. Synthesis  2009,  165 
  • 16b Pradhan R. Patra M. Behera AK. Mishrab BK. Behera RK. Tetrahedron  2006,  62:  779 
    Suche in Google Scholar
  • 17a Loev B. Goodman MM. Snader KM. Tedeschi R. Macko E. J. Med. Chem.  1974,  19:  956 
    Suche in Google Scholar
  • 17b Mager PP. Coburn RA. Solo AJ. Triggle DJ. Rothe H. Drug Des. Discovery  1992,  8:  273 
    Suche in Google Scholar
  • 18 Safak C. Simsek R. Mini-Rev. Med. Chem.  2006,  6:  747 
    CrossrefPubMedSuche in Google Scholar
  • 19a Mao Y.-Z. Jin M.-Z. Liu Z.-L. Wu L.-M. Org. Lett.  2000,  2:  741 
    Suche in Google Scholar
  • 19b Charette AB. Mathieu S. Martel J. Org. Lett.  2005,  7:  5401 
    Suche in Google Scholar
  • 19c Chen J. McNeil AJ. J. Am. Chem. Soc.  2008,  130:  16496 
    Suche in Google Scholar
  • 20 Hantzsch A. Justus Liebigs Ann. Chem.  1882,  215:  1 
    CrossrefSuche in Google Scholar
  • 21a Moore JA. Kim JH. Tetrahedron Lett.  1991,  32:  3449 
    Suche in Google Scholar
  • 21b Kim JH. Moore JA. Macromolecules  1993,  26:  3510 
    Suche in Google Scholar
  • 23 Huang Z.-T. Liu Z.-R. Synth. Commun.  1989,  19:  943 
    CrossrefSuche in Google Scholar
22

General Procedure for the Synthesis of 3: Heterocyclic ketene aminals 1 (1 mmol) and 2-[3-oxoisobenzofuran-1 (3H)-ylidene]malononitrile (2; 1 mmol) were stirred in DMF (5 mL) at 120 ˚C until the reaction was complete as monitored by TLC (ca. 2-12 h). After the reaction mixture was cooled to r.t., the solvents were removed in vacuo and the resulting solids were subjected to recrystallization (MeOH-Et2O or MeCN) to provide the desired fused heterospiro compounds 3.
Compound 3f: yellow solid; mp 306-307 ˚C. IR (KBr): 3363 (m), 3331 (m), 2211 (m), 1633 (s), 1603 (s), 1582 (s), 1558 (s), 1508 (m), 1370 (s), 1311 (s), 931 (m), 849 (w), 763 (m), 732 (m), 678 (m), 652 (m) cm-¹. ¹H NMR (300 MHz, DMSO-d 6): δ = 7.73 (d, J = 7.5 Hz, 1 H), 7.53-7.63 (m, 4 H), 7.44-7.47 (m, 4 H), 7.30-7.40 (m, 2 H), 7.20-7.25 (m, 1 H), 7.04 (d, J = 7.2 Hz, 1 H), 4.03-4.22 (m, 2 H), 3.79-3.94 (m, 2 H). ¹³C NMR (75 MHz, DMSO-d 6): δ = 192.0, 166.8, 154.4, 152.7, 142.9, 139.2, 137.7, 132.5, 137.0, 130.6, 130.2, 129.5, 129.1, 128.9, 128.3, 128.0, 126.7, 125.8, 117.1, 105.1, 77.9, 48.6, 45.4. HRMS (ESI): m/z [M + H]+ calcd for C28H21N4O3 +: 461.1608; found: 461.1609. Compound 3o: yellow solid; mp 205-207 ˚C. IR (KBr): 3282 (m), 3061 (m), 2212 (m), 1631 (s), 1604 (s), 1560 (s), 1528 (s), 1480 (m), 1376 (s), 1337 (s), 1280 (m), 1068 (m), 927 (m), 850 (m), 776 (m), 676 (m) cm-¹. ¹H NMR (300 MHz, DMSO-d 6): δ = 7.63 (d, J = 6.9 Hz, 1 H), 7.17-7.31 (m, 6 H), 7.00 (d, J = 6.6 Hz, 1 H), 4.01-4.02 (m, 2 H), 3.40-3.42 (m, 2 H), 2.00-2.03 (m, 2 H). ¹³C NMR (75 MHz, DMSO-d 6): δ = 192.7, 166.8, 156.1, 154.5, 152.1, 139.7, 137.2, 132.4, 130.6, 130.2, 130.1, 129.9, 128.5, 124.2, 117.2, 103.2, 83.5, 48.6, 42.8, 18.6. HRMS (ESI): m/z [M + H]+ calcd for C23H18N4O3Br+: 477.0571; found: 477.0562.