One-Pot Three-Component Synthesis of 3-Amino-5,8-dioxo-5,8-dihydro-1H-pyrazolo[1,2-a]pyridazines

Abstract

The reactive 1:1 zwitterionic intermediate formed by the addition of isocyanides to dialkyl acetylenedicarboxylates was trapped by 3,6-dihydroxypyridazine to produce 3-amino-5,8-dioxo-5,8-dihydro-1H-pyrazolo[1,2-a]pyridazines in good yields.

Key words

multicomponent reactions - pyrazolo[1,2-a]pyrid­azines - isocyanides - cyclizations - heterocycles

References

• 1 Ugi I. Angew. Chem., Int. Ed. Engl.  1982,  21:  810 
• 2 Dömling A. Chem. Rev.  2006,  106:  17 
• 3 Dömling A. Ugi I. Angew. Chem. Int. Ed.  2000,  39:  3168 
• 4 Weber L. Curr. Med. Chem.  2002,  9:  2085 
• 5 Swinbourne JF. Hunt HJ. Klinkert G. Adv. Heterocycl. Chem.  1987,  23:  103 
• 6 Radl S. In Comprehensive Heterocyclic Chemistry II   Vol. 8:  Katritzky AR. Rees CW. Scriven EVF. Pergamon Press; London: 1996.  Chap. 31. p.747-832  ; and references therein
• 7 . Malik S. Cun-heng H. Clardy J. Tetrahedron Lett.  1985,  26:  2759 
• 8 Clark MP, Laufersweiler MJ, Djung JF.-J, and . inventors; US Patent  6821971. 
• 9 Al’-Assar F. Zelenin KN. Lesiovskaya EE. Bezhan IP. Chakchir BA. Pharm. Chem. J.  2002,  36:  598 
• 10 Jungheim LN. Boyd DB. Indelicato JM. Pasini CE. Preston DA. Alborn WE. J. Med. Chem.  1991,  34:  1732 
• 11 Wagner-Jauregg T. Fischer J. Arzneim.-Forsch.  1970,  20:  831 
• 12a Liu B. Brandt JD. Moeller KD. Tetrahedron  2003,  59:  8515 
• 12b Curtis MD. Hayes NC. Matson PA. J. Org. Chem.  2006,  71:  5035 
• 13 Aeberli P. Houlihan WJ. J. Org. Chem.  1969,  34:  2720 
• 14 Lawton G. Moody CJ. Pearson CJ. J. Chem. Soc., Perkin Trans. 1  1987,  877 
• 15 Rutjes FPJT. Udding JH. Hiemstra H. Speckamp WN. Recl. Trav. Chim. Pays-Bas  1994,  113:  145 
• 16 Wasserman HH. Robinson RP. Matsuyama H. Tetrahedron Lett.  1980,  21:  3493 
• 17 Darwen SP. Smalley RK. Tetrahedron Lett.  1985,  26:  5707 
• 19 Ugi I. Isonitrile Chemistry   Academic Press; London: 1971. 
• 20 Nair V. Deepthi A. Tetrahedron Lett.  2006,  47:  2037 
• 21 Walborsky HM. Periasamy MP. In The Chemistry of Functional Groups, Supplement C   Patai S. Rappaport Z. Wiley; New York: 1983.  Chap. 20. p.835-837  

18

Selected X-ray crystallographic data for compound 8d: C₁₅H₁₉N₃O₆, M _r 337.33; crystal size: 0.4 × 0.3 × 0.2 mm; crystal system: triclinic; a = 8.882 (3), b = 10.0398 (13), c = 10.730 (3) Å, α = 71.481 (18), β = 67.10 (3), γ = 81.148 (17)°; space group P-1; Z = 2, V = 835.3 (4) ų, D _calc. = 1.341 g cm^-3; R = 0.0446, R _w = 0.1258; -11 ≤ h ≤ 6; -12 ≤ k ≤ 12; -13 ≤ l ≤ 12; MoK _α radiation (λ = 0.71073 Å); T = 290 (2) K. CCDC 630958 contains the supplementary crystallographic data of compound 8d. These data can be obtained free of charge from The Cambridge Crystallographic Data Centre via the internet (http://www.ccdc.cam.ac.uk/data_request/cif), e-mail ([e-mail]), or fax [phone]).