High-throughput synthesis of N3-acylated dihydropyrimidines combining microwave-assisted synthesis and scavenging techniques

Organic Letters

Volumn 5, Issue 8, 2003, Pages 1205-1208

  Dallinger, Doris ^a   Gorobets, Nikolay Yu ^a   Kappe, C Oliver ^a  

^a UNIVERSITY OF GRAZ   (Austria)

Author keywords

[No Author keywords available]

Indexed keywords

ACID ANHYDRIDE; DIAMINE; POLYSTYRENE; PYRIMIDINE DERIVATIVE; SILICON DIOXIDE; WATER;

ACYLATION; ARTICLE; EXTRACTION; HEATING; MICROWAVE IRRADIATION; PURIFICATION; SYNTHESIS; TECHNIQUE;

EID: 0141740762     PISSN: 15237060     EISSN: None     Source Type: Journal    
DOI: 10.1021/ol034085v     Document Type: Article

References (32)

1. (a) Lew, A.; Krutzik, P. O.; Hart, M. E.; Chamberlin, A. R. J. Comb. Chem. 2002, 4, 95-105.
2. (b) Kappe, C. O. Curr. Opin. Chem. Biol. 2002, 6, 314-320.
3. (c) Lidstrom, P.; Westman, J.; Lewis, A. Comb. Chem. High Throughput Screen. 2002, 5, 441-458.
4. (d) For general information and references on microwave-assisted organic synthesis, see http://www.maos.net.
5. (a) Finaru, A.; Berthault, A.; Besson, T.; Guillaumet, G.; Berteina-Raboin, S. Org. Lett. 2002, 4, 2613-2615.
6. (b) Austin, R. E.; Okonya, J. F.; Bond, D. R. S.; Al-Obeidi, F. Tetrahedron Lett. 2002, 43, 6169-6171.
7. (c) Erdélyi, M.; Gogoll, A. Synthesis 2002, 1592-1596.
8. (d) Olivos, H. J.; Alluri, P. G.; Reddy, M. M.; Salony, D.; Kodadek, T. Org. Lett. 2002, 4, 4057-4059.
9. (e) Perez, R.; Beryozkina, T.; Zbruyev, O. I.; Haas, W.; Kappe, C. O. J. Comb. Chem. 2002, 4, 501-510.
10. (a) Ley, S. V.; Taylor, S. Bioorg. Med. Chem. Lett. 2002, 12, 1813-1816.
11. (b) Baxendale, I. R.; Lee, A.-I.; Ley, S. V. J. Chem. Soc., Perkin Trans. 1 2002, 1850-1857.
12. (c) Launay, D.; Booth, S.; Clemens, I.; Merritt, A.; Bradley, M. Tetrahedron Lett. 2002, 43, 7201-7203.
13. (d) Petricci, E.; Botta, M.; Corelli, F.; Mugnaini, C. Tetrahedron Lett. 2002, 43, 6507-6509.
14. (e) Crosignani, S.; White, P. D.; Linclau, B. Org. Lett. 2002, 4, 2961-2963.
15. (a) Wu, C.-Y.; Sun, C.-M. Synlett 2002, 1709-1711.
16. (b) Bendale, P. M.; Sun, C.-M. J. Comb. Chem. 2002, 4, 359-361.
17. (a) Coleman, C. M.; MacElroy, J. M. D.; Gallagher, J. F.; O'Shea, D. F. J. Comb. Chem. 2002, 4, 87-93.
18. (b) Strohmeier, G.; Kappe, C. O. J. Comb. Chem. 2002, 4, 154-161.
19. Stadler, A.; Kappe, C. O. J. Comb. Chem. 2001, 3, 624-630.
20. (a) Booth, J. R.; Hodges, J. C. Acc. Chem. Res. 1999, 32, 18-26.
21. (b) Ley, S. V.; Baxendale, I. R.; Bream, R. N.; Jackson, P. S.; Leach, A. G.; Longbottom, D. A.; Nesi, M.; Scott, J. S.; Storer, I.; Taylor, S. J. J. Chem. Soc., Perkin Trans. 1 2000, 3815-4196.
22. (c) Kirschning, A.; Monenschein, H.; Wittenberg, R. Angew. Chem., Int. Ed. 2001, 40, 650-679.
23. (d) Eames, J.; Watkinson, M. Eur. J. Org. Chem. 2001, 1213-1224.
24. (e) Tschucke, C. C.; Markert, C.; Bannwarth, W.; Roller, S.; Hebel, A.; Haag, R. Angew. Chem., Int. Ed. 2002, 41, 3964-4000.
25. Kappe, C. O. Acc. Chem. Res. 2000, 33, 879-888.
26. Kappe, C. O. Tetrahedron 1993, 49, 6937-6963 and references therein.
27. (a) Palmacci, E. R.; Hewitt, M. C.; Seeberger, P. H. Angew. Chem., Int. Ed. 2001, 40, 4433-4436.
28. (b) McComas, W.; Chen, L.; Kim, K. Tetrahedron Lett. 2000, 41, 3573-3576.
29. (c) Thompson, L. A.; Combs, A. P.; Trainor, G. L.; Wang, Q.; Langlois, T. J.; Kirkland, J. J. Comb. Chem. High Throughput Screen. 2000, 3, 107-115.
30. The higher reactivity of the acyl group at N1 (in comparison to the N3 acyl group) can be rationalized considering the fact that the N1 acyl group is in conjugation with the ester functionality at C5, thereby representing a masked vinylogous triacylamine system. Bis-acylated and mixed N1/N3-acyl DHPMs can conveniently be synthesized employing the more reactive acid chlorides as acylation reagents (for details, see the Supporting Information).
31. All microwave irradiation experiments were carried out with a dedicated single-mode instrument with integrated robotics capable of automated dispensing of liquid reagents into the microwave process vials through a septum and automated sequential microwave processing of individual reaction vials. For details, see ref 6.
32. Detailed procedures for the all individual processing steps are provided in the Supporting Information.