Dowex-promoted general synthesis of N,N′-disubstituted-4-aryl-3,4-dihydropyrimidinones using a solvent-free Biginelli condensation protocol

Tetrahedron Letters

Volumn 47, Issue 25, 2006, Pages 4205-4207

  Singh, Kamaljit ^a   Arora, Divya ^a   Singh, Sukhdeep ^a  

^a GURU NANAK DEV UNIVERSITY   (India)

Author keywords

Biginelli compounds; Calcium channel modulators; DHPMs; Dowex; Solvent free synthesis

Indexed keywords

1,3 DIMETHYLUREA; ALDEHYDE; PYRIMIDINONE DERIVATIVE; UNCLASSIFIED DRUG; UREA DERIVATIVE;

ARTICLE; DRUG SYNTHESIS; ION EXCHANGE; POLYMERIZATION; SUBSTITUTION REACTION;

EID: 33646502807     PISSN: 00404039     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.tetlet.2006.04.061     Document Type: Article

References (14)

1. Kappe C.O. Eur. J. Med. Chem. 35 (2000) 1043-1052
2. Rovnyak G.C., Atwal K.S., Hedberg A., Kimball S.D., Moreland S., Gougoutas J.Z., O'Reilly B.C., Schwartz J., and Malley M.F. J. Med. Chem. 35 (1992) 3254-3263
3. Biginelli P. Gazz. Chim. Ital. 23 (1893) 360-413
4. Kappe C.O. Tetrahedron 49 (1993) 6937-6963
5. Kappe C.O., and Stadler A. Org. React. 63 (2004) 1-117
6. Wipf P., and Cunningham A. Tetrahedron Lett. 36 (1995) 7819-7822
7. Studer A., Jeger P., Wipf P., and Curran D.P. J. Org. Chem. 82 (1997) 2917-2924
8. Singh K., Singh S., and Mahajan A. J. Org. Chem. 70 (2005) 6114-6117
9. Ranu B.C., Hajra A., and Dey S.S. Org. Process. Res. Dev. 6 (2002) 817-818
10. Jenner G. Tetrahedron Lett. 45 (2004) 6195-6198
11. Typical procedure: A mixture of p-nitrobenzaldehyde (3.02 g, 20.0 mmol), ethyl acetoacetate (2.60 g, 20 mmol), N,N′-dimethylurea (1.76 g, 20 mmol) and Dowex-50W (Aldrich Chemical Company) (100 mg) in a glass test tube was heated for 3 h at 130 °C, in an oil bath. After cooling to room temperature, the reaction was dissolved in ethyl acetate and Dowex-50W was removed by filtration. The filtrate was concentrated under reduced pressure. Recrystallization from dichloromethane gave pure 4g. For 50 mmol reactions, the quantity of Dowex-50W was increased to 200 mg. All compounds exhibited satisfactory spectral and microanalytical data (kindly see Supplementary data).
12. Singh K., Singh S., and Kaur P. Lett. Org. Chem. 3 (2006) 201-203
13. Salehi P., Dabiri M., Zolfigol M.A., and Fard M.A.B. Tetrahedron Lett. 44 (2003) 2889-2891
14. Kappe C.O., Kumar D., and Verma R.S. Synthesis (1999) 1799-1803