Subscribe to RSS
Please copy the URL and add it into your RSS Feed Reader.
https://www.thieme-connect.de/rss/thieme/en/10.1055-s-00000084.xml
Synthesis 2014; 46(07): 947-954
DOI: 10.1055/s-0033-1340664
DOI: 10.1055/s-0033-1340664
paper
Mild and Direct Access to 7-Substituted-4-trifluoromethylpyrimido[1,2-b]pyridazin-2-one Systems
Further Information
Publication History
Received: 18 November 2013
Accepted after revision: 20 December 2013
Publication Date:
30 January 2014 (online)

Abstract
New and efficient methods for the synthesis of 7-substituted-4-trifluoromethylpyrimido[1,2-b]pyridazin-2-one derivatives using either two-step Suzuki/heterocyclization, or two-step heterocyclization/substitution sequences are developed. A variety of substituted products are obtained in good to excellent yields from 3-amino-6-chloropyridazine and ethyl 4,4,4-trifluorobut-2-ynoate.
Key words
ethyl 4,4,4-trifluorobutynoate - aminopyridazine - heterocyclization - trifluoromethylpyrimido[1,2-b]pyridazin-2-one - Suzuki reactionSupporting Information
- for this article is available online at http://www.thieme-connect.com/ejournals/toc/synthesis.
- Supporting Information
-
References
- 1 Cox JM, Harper B, Mastracchio A, Leiting B, Roy RS, Patel RA, Wu JK, Lyons KA, He H, Xu S, Zhu B, Thornberry NA, Weber AE, Edmondson SD. Bioorg. Med. Chem. Lett. 2007; 17: 4579
- 2 Kettle JG, Brown S, Crafter C, Davies BR, Dudley P, Fairley G, Faulder P, Fillery S, Greenwood H, Hawkins J, James M, Johnson K, Lane CD, Pass M, Pink JH, Plant H, Cosulich SC. J. Med. Chem. 2012; 55: 1261
- 3 Ewan K, Pajak B, Stubbs M, Todd H, Barbeau O, Quevedo C, Botfield H, Young R, Ruddle R, Samuel L, Battersby A, Raynaud F, Allen N, Wilson S, Latinkic B, Workman P, McDonald E, Blagg J, Aherne W, Dale T. Cancer Res. 2010; 70: 5963
- 4 Juderna JG, Skiles RD, Pilgram K. J. Org. Chem. 1971; 36: 3506
- 5 Mátyus P, Kasztreiner E, Szilágyi G, Sóti M. Heterocycles 1983; 20: 2225
- 6 Mátyus P, Szilágyi G, Kasztreiner E, Rabloczky G. J. Heterocycl. Chem. 1988; 25: 1535
- 7 Pollak A, Stanovnik B, Tisler M. J. Org. Chem. 1971; 36: 245 ; this report described access to pyrimido[1,2-b]pyrid-azin-2-ones, but the structures were subsequently revised to pyrimido[1,2-b]pyridazin-4-ones
- 8 Ojima I. Fluorine in Medicinal Chemistry and Chemical Biology. Wiley-Blackwell; Chichester: 2009
- 9 Purser S, Moore PR, Swallow S, Gouverneur V. Chem. Soc. Rev. 2008; 37: 320
- 10 Müller K, Faeh C, Diederich F. Science 2007; 317: 1881
- 11 Hamper BC. Org. Synth. 1991; 70: 246
- 12 Prié G, Thibonnet J, Abarbri M, Duchêne A, Parrain J.-L. Synlett 1998; 839
- 13 Thibonnet J, Prié G, Abarbri M, Duchêne A, Parrain J.-L. Tetrahedron Lett. 1999; 40: 3151
- 14 Carcenac Y, Zine K, Kizirian J.-C, Thibonnet J, Duchene A, Parrain J.-L, Abarbri M. Adv. Synth. Catal. 2010; 352: 949
- 15 Zine K, Petrignet J, Thibonnet J, Abarbri M. Synlett 2012; 23: 755
- 16 Richard S, Prié G, Guignard A, Thibonnet J, Parrain J.-L, Duchêne A, Abarbri M. Helv. Chim. Acta 2003; 86: 726
- 17 Prié G, Richard S, Parrain J.-L, Duchêne A, Abarbri M. J. Fluorine Chem. 2002; 117: 35
- 18 Zeng J, Tan YT, Leown ML, Liu X.-W. Org. Lett. 2012; 14: 4386
- 19 Harriman GC. B, Chi S, Zhang M, Crowe A, Bennett RA, Parsons I. Tetrahedron Lett. 2003; 44: 3659
- 20 Maes BU. W, Lemière GL. F, Dommisse R, Augustyns K, Hammers A. Tetrahedron 2000; 56: 1777
- 21 Guery S, Parrot I, Rival Y, Wermuth CG. Tetrahedron Lett. 2001; 42: 2115
- 22 Gavande N, Johnston GA. R, Hanrahan JR, Chebib M. Org. Biomol. Chem. 2010; 8: 4131
- 23 Iqbal F, Ellwood R, Mortensen M, Smart TG, Baker JR. Bioorg. Med. Chem. Lett. 2011; 21: 4252
- 24 Steck EA, Brundage RP, Fletcher LT. J. Am. Chem. Soc. 1954; 76: 3225
- 25 Maes BU. W, Lemière GF, Domisse R, Augustyns K, Haemers A. Tetrahedron 2000; 56: 1777
- 26 Steck EA, Brundage RP, Fletcher LT. J. Heterocycl. Chem. 1975; 12: 1009
- 27 The very low solubility of compounds 9c and 9h prevented us from recording useful 13C NMR spectra, even after 10 h of accumulation. However, copies of the 1H and 19F NMR spectra of these compounds are available in the Supporting Information.