Synthesis of Original Trifluoromethylated 6-Aryl-pyridazines Fused with Thiazolidine or 1,2,4-Triazole

Abstract

An efficient synthesis of original 8-trifluoromethyl-7H-thiazolo[3,2-b]- and 1,2,4-triazolo[4,3-b]pyridazines is described. Starting from the 4-trifluoromethyl-4,5-dihydropyridazin-3-one, the methodology involves a five-membered ring closure, based on the reaction of a bis(electrophilic) reagent with an exocyclic heteroatom linked to position 3 and the endocyclic nitrogen at position 2 of the pyridazine nucleus.

Key words

fluorine - nitrogen heterocycles - pyridazine derivatives - thiazolo[3,2-b]pyridazine - 1,2,4-triazolo[4,3-b]pyridazine

References

• 2a Albright JD. Moran DB. Wright WB. Collins JB. Beer B. Lippa AS. Greenblatt EN. J. Med. Chem.  1981,  24:  592 
• 2b Sircar I. J. Heterocycl. Chem.  1985,  22:  1045 
• 3 Allen GR, Hanifin JW, Moran DB, and Albright JD. inventors; US Pat.  4,293,554.  ; Chem. Abstr. , 96, 866
• 4 Welch JT. Eswarakrishnan S. Fluorine in Bioorganic Chemistry   Wiley; New York: 1991. 
• 5 Lippa AS. Coupet J. Greenblatt EN. Klepner CA. Beer B. Pharmacol., Biochem. Behav.  1979,  11:  99 
• 6 Joshi KC. Dubey K. Pharmazie  1979,  34:  801 
• 7a Our method: Brulé C. Bouillon J.-P. Nicolaï E. Portella C. Synthesis  2003,  436 
• 7b Very recently, a new procedure for the preparation of 4-trifluoromethyl pyridazin-3-ones was reported: Sibgatulin D. A. Volochnyuk D. M. Kostyuk A. N. Synlett  2005,  1907 
• 8 Lieberman DF. Albright JD. J. Heterocycl. Chem.  1988,  25:  827 
• 9 Cava MP. Levinson MI. Tetrahedron  1985,  41:  5061 
• 10 Potts KT. Bordeaux KG. Kuehnling WR. Salsbury RL. J. Org. Chem.  1985,  50:  1677 
• 11a Badr MZA. El-Sherief HA. El-Naggar GM. Mahgoub SA. J. Heterocycl. Chem.  1984,  21:  471 
• 11b Daunis J. Guerret-Rigail M. Jacquier R. Bull. Soc. Chim. Fr.  1971,  3043 
• 12 Moreau S. Coudert P. Rubat C. Gardette D. Vallee-Goyet D. Couquelet J. Bastide P. Tronche P. J. Med. Chem.  1994,  37:  2153 

1

Current address: Laboratoire Synthèse et Chromatographie, SMS-EA 3233, Université de Rouen, IRCOF, 76821 Mont S^t-Aignan Cedex, France.