New Efficient Synthesis of 2-Substituted Benzothieno[3,2-d]pyrimidin-4(3H)-ones via a Tandem Aza-Wittig Reaction

 

 Buy Article Permissions and Reprints All articles of this category

Abstract

1-Aryl-3-[2-(ethoxycarbonyl)benzothien-3-yl]carbodiimides 4, obtained from aza-Wittig reactions of iminophosphorane 3 with aryl isocyanates, reacted with secondary amines, phenols, or alkanols in the presence of a catalytic amount of potassium carbonate or sodium alkoxide to give 2-substituted benzothieno[3,2-d]pyrimidin-4(3H)-ones 6 in good yields. The reaction of carbodiimides 4 with primary amines RNH₂ (R ≠ H, Me) in the presence of sodium ethoxide selectively produced one regioisomer 8 via a base-catalyzed cyclization mechanism. However, a different regioisomer 9 was obtained when primary amines RNH₂ (R = H, Me) were used in the absence of sodium ethoxide via a direct cyclization mechanism.

References

• 1 Purines in Cellular Signaling: Targets for New Drugs   Jacobson KA. Daly JW. Manganiello V. Springer Verlag; New York: 1990. 
  Google Scholar
• 2 Walter H. inventors; WO  9914202.  ; Chem. Abstr. 1999, 130, 252368
• 3 Chambhare RV. Khadse BG. Bobde AS. Bahekar RH. Eur. J. Med. Chem.  2003,  38:  89 
  CrossrefPubMedGoogle Scholar
• 4 Taguchi M, Ota T, and Hatayama K. inventors; WO  9303040.  ; Chem. Abstr., 1993, 119, 160309
• 5 Shishoo CJ. Shirsath VS. Rathod IS. Yande VD. Eur. J. Med. Chem.  2000,  35:  351 
  CrossrefPubMedGoogle Scholar
• 6 De Laszlo SE, Patchett AA, Allen EE, and Greenlee WJ. inventors; EP  0502725.  ; Chem. Abstr. 1992, 118, 22249
• 7 Eggenweiler HM, and Eiermann V. inventors; WO  2002049649.  ; Chem. Abstr. 2002, 137, 47217
• 8 Nomoto Y. Takai H. Ohno T. Kubo K. Chem. Pharm. Bull.  1991,  39:  352 
  CrossrefGoogle Scholar
• 9 Meyer MD, Altenbach RJ, Basha FZ, Carroll WA, Drizin I, Elmore SW, Kerwin JF, Lebold SA, Lee EL, Sippy KB, Tietje KR, and Wendt MD. inventors; US  5597823.  ; Chem. Abstr. 1997, 126, 199575
• 10 Ehrlich PP, Ralston JW, Daanen JF, and Meyer MD. inventors; WO  9957122.  ; Chem. Abstr. 1999, 131, 337029
• 11 Bridges AJ. Zhou H. J. Heterocycl. Chem.  1997,  34:  1163 
  CrossrefGoogle Scholar
• 12 El-Telbany F. Hutchins RO. J. Heterocycl. Chem.  1985,  22:  401 
  CrossrefGoogle Scholar
• 13 Robba M. Touzot P. El-Kashef H. J. Heterocycl. Chem.  1980,  17:  923 
  CrossrefGoogle Scholar
• 14 Blackburn C. Achab A. Elder A. Ghosh S. Guo J. Harriman G. Jones M. J. Org. Chem.  2005,  70:  10206 
  CrossrefGoogle Scholar
• 15 Izquierdo I. Plaza MT. Rodríguez M. Franco F. Martos A. Tetrahedron  2005,  61:  11697 
  CrossrefGoogle Scholar
• 16 Palacios F. Alonso C. Rodríguez M. Martinez de Marigorta E. Rubiales G. Eur. J. Org. Chem.  2005,  1795 
  Google Scholar
• 17 Braese S. Gil C. Knepper K. Zimmermann V. Angew. Chem. Int. Ed.  2005,  44:  5188 
  CrossrefPubMedGoogle Scholar
• 18 Ding MW. Xu SZ. Zhao JF. J. Org. Chem.  2004,  69:  8366 
  CrossrefGoogle Scholar
• 19 Ding MW. Chen YF. Huang NY. Eur. J. Org. Chem.  2004,  3872 
  CrossrefGoogle Scholar
• 20 Zhao JF. Xie C. Xu SZ. Ding MW. Xiao WJ. Org. Biomol. Chem.  2006,  4:  130 
  CrossrefGoogle Scholar
• 21 Ding MW. Fu BQ. Cheng L. Synthesis  2004,  1067 
  Article in Thieme ConnectGoogle Scholar
• 22 De Angelis GG, and Hess H.-JE. inventors; US  3706747.  ; Chem. Abstr. 1973, 78, 72187z
• 23 Zhao JF. Xie C. Ding MW. He HW. Chem. Lett.  2005,  34:  1022 
  CrossrefGoogle Scholar