Summary.
Although various thiazoles are known in literature for their biological and pharmacological properties only a few multi-step synthesis pathways for the preparation of thiazolo[3,2-a]pyrimidinones have been reported, which are tedious and time-consuming. An alternative synthesis pathway is described, which allows the preparation of 2,3-dihydrothiazolo[3,2-a]pyrimidin-5-ones in a one-step process based on a Michael-type tandem reaction. By heating of 2-thiobarbituric acid with ethyl 4-bromocrotonate in ethanol at 60°C for 2 h, a 2,3-dihydrothiazolo[3,2-a]pyrimidin-5-one was obtained in 73% yield, whereas carrying out the reaction at room temperature results in the formation of an unstable unsaturated ester. The structures of both, the α,β-unsaturated ester as well as the 2,3-dihydrothiazolo[3,2-a]pyrimidin-5-one were confirmed by NMR spectroscopy. Additionally, the structure of the 2,3-dihydrothiazolo[3,2-a]pyrimidin-5-one was investigated by single-crystal X-ray analysis. The described approach offers a significant improvement over previously reported synthesis pathways because it allows the simple preparation of 2,3-dihydrothiazolo[3,2-a]pyrimidin-5-ones with good yields in a one-step reaction.
Similar content being viewed by others
References
G Doria C Passerotti R Sala R Magrini P Sberze M Tibolla R Ceserani G Arcari R Castello D Doti (1985) Farmaco Ed Sci 40 885 Occurrence Handle1:CAS:528:DyaL28XmtFKrsw%3D%3D
SC Bell PHL Wei (1976) J Med Chem 19 524 Occurrence Handle1:CAS:528:DyaE28XhtlShsbY%3D Occurrence Handle10.1021/jm00226a016
Seperic Neth Appl (1976) 7600: 885
J Baetz (1973) Br Pat 1 334 628
M Di Braccio G Roma M Mazzei A Balbi R Testa (1986) Farmaco Ed Sci 41 183 Occurrence Handle1:CAS:528:DyaL28XmtVyrsLs%3D
E Jeanneau-Nicolle M Benoit-Guyod A Namil G Leclerc (1992) Eur J Med Chem 27 115 Occurrence Handle1:CAS:528:DyaK38XksVyntbc%3D Occurrence Handle10.1016/0223-5234(92)90099-M
K Danel EB Pedersen C Nielsen (1998) J Med Chem 41 191 Occurrence Handle1:CAS:528:DyaK1cXptFGm Occurrence Handle10.1021/jm970443m
EJ Masters MT Bogert (1942) J Am Chem Soc 64 2709 Occurrence Handle1:CAS:528:DyaH3sXjs1an Occurrence Handle10.1021/ja01263a052
RA Glennon RG Bass E Schubert (1979) J Heterocyclic Chem 16 903 Occurrence Handle1:CAS:528:DyaL3cXit1Cmsg%3D%3D
U Niedballa H Vorbrüggen (1974) J Org Chem 39 3654 Occurrence Handle1:CAS:528:DyaE2MXhslSmsg%3D%3D Occurrence Handle10.1021/jo00939a008
C Dreyer G Krey H Keller F Givel G Helftenbein W Wahli (1992) Cell 33 879 Occurrence Handle10.1016/0092-8674(92)90031-7
J Berger DE Moller (2002) Annu Rev Med 53 409 Occurrence Handle1:CAS:528:DC%2BD38Xitl2mt7s%3D Occurrence Handle10.1146/annurev.med.53.082901.104018
TM Willson PJ Brown DD Sternbach BR Henke (2000) J Med Chem 43 IssueID4 527 Occurrence Handle1:CAS:528:DC%2BD3cXht1Churk%3D Occurrence Handle10.1021/jm990554g
BM Forman J Chen RM Evans (1997) Proc Natl Acad Sci USA 94 4312 Occurrence Handle1:CAS:528:DyaK2sXjtVyhsbs%3D Occurrence Handle10.1073/pnas.94.9.4312
SA Kliewer BM Forman B Blumberg ES Ong U Borgmeyer DJ Mangelsdorf K Uemesono RM Evans (1994) Proc Natl Acad Sci USA 91 7355 Occurrence Handle1:CAS:528:DyaK2cXmsFajtb0%3D Occurrence Handle10.1073/pnas.91.15.7355
K Yu W Bayona CB Kallen HP Harding CP Ravera G McMahon M Brown MA Lazar (1995) J Biol Chem 270 23975 Occurrence Handle1:CAS:528:DyaK2MXovVSgsbk%3D Occurrence Handle10.1074/jbc.270.41.23975
G d’Atri P Gomarasca G Resnati G Tronconi C Scolastico CR Sirtori (1984) J Med Chem 27 1621 Occurrence Handle1:CAS:528:DyaL2cXmtlSnurs%3D Occurrence Handle10.1021/jm00378a016
MM Campbell SJ Mickel G Singh (1991) Bioorg Med Chem Lett 1 IssueID5 247 Occurrence Handle1:CAS:528:DyaK3MXmsVOrtbg%3D Occurrence Handle10.1016/S0960-894X(01)81035-0
YL Zborovskii VV Orysyk AA Dobosh VI Staninets VV Pirozhenko AN Chernega (2003) Chem Heterocycl Compd 39 IssueID8 1099 Occurrence Handle1:CAS:528:DC%2BD2cXhsFantrg%3D Occurrence Handle10.1023/B:COHC.0000003532.58469.cc
NY Slivka YI Geveza VI Staninets (2004) Chem Heterocycl Compd 40 IssueID5 660 Occurrence Handle1:CAS:528:DC%2BD2cXptVKmsL8%3D Occurrence Handle10.1023/B:COHC.0000037323.22839.9f
AI Vaskevich RI Gevaza RI Vaskevich VI Staninets (2004) Chem Heterocycl Compd 40 IssueID8 1087 Occurrence Handle1:CAS:528:DC%2BD2MXns1Ogtg%3D%3D Occurrence Handle10.1023/B:COHC.0000046702.48941.53
E Campaigne JC Huffman R Yodice (1981) J Heterocyclic Chem 18 575 Occurrence Handle1:CAS:528:DyaL3MXltFGntrk%3D Occurrence Handle10.1002/jhet.5570180328
JN Low G Ferguson M Melguizo A Sanchez (1999) Acta Cryst C55 IUC9900048
U Rychlewska (1980) Acta Cryst B36 971 Occurrence Handle1:CAS:528:DyaL3cXitVOgtLg%3D
CCDC 264399 (17) contains the supplementary crystallographic data for this paper. These data can be obtained free of charge via www.ccdc.cam.ac.uk/conts/retrieving.html (or from the Cambridge Crystallographic Data Centre, 12 Union Road, Cambridge CB2 1EZ, UK; Fax: (+44) 1223-336-033; e-mail: deposit@ccdc.cam.ac.uk)
AH Pande D Moe KN Nemec S Qin S Tan SA Tatulian (2004) Biochemistry 43 IssueID46 14653 Occurrence Handle1:CAS:528:DC%2BD2cXptVyrur4%3D Occurrence Handle10.1021/bi048775y
O Werz D Szellas M Henseler D Steinhilber (1998) Mol Pharmacol 54 445 Occurrence Handle1:CAS:528:DyaK1cXlsVWlsLo%3D
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Syha, Y., Valmalle, C., Bats, J. et al. Synthesis of 2,3-Dihydrothiazolo[3,2-a]pyrimidin-5-ones by a Michael-type Tandem Reaction. Monatsh. Chem. 137, 1357–1364 (2006). https://doi.org/10.1007/s00706-006-0531-z
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00706-006-0531-z