An efficient protocol for solid phase aminothiazole synthesis

Tetrahedron Letters

Volumn 47, Issue 35, 2006, Pages 6179-6182

  Sreejalekshmi, Kumaran G ^a   Devi, Satyabhama K C ^a   Rajasekharan, Kallikat N ^a  

^a UNIVERSITY OF KERALA   (India)

Author keywords

2,4 Diamino 5 ketothiazoles; Aminomethylpolystyrene; Solid phase synthesis; Thiocarbamoylamidine transfer; Traceless cleavage

Indexed keywords

HALOKETONE; POLYMER; THIAZOLE DERIVATIVE;

ARTICLE; AUTOMATION; CHEMICAL REACTION; COMBINATORIAL CHEMISTRY; DRUG DESIGN; DRUG STRUCTURE; DRUG SYNTHESIS; SOLID PHASE SYNTHESIS; STRUCTURE ANALYSIS;

EID: 33746271615     PISSN: 00404039     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.tetlet.2006.06.169     Document Type: Article

References (32)

1. Thompson L.A., and Ellman J.A. Chem. Rev. 96 (1996) 555-560
2. Balkenhohl F., Bussche-Hünnefeld C., Lansky A., and Zechel C. Angew. Chem., Int. Ed. 35 (1996) 2288-2337
3. Bailey N., Dean A.W., Judd D.B., Middlemiss D., Storer R., and Watson S.P. Bioorg. Med. Chem. Lett. 6 (1996) 1409-1414
4. Hargrave K.D., Hess F.K., and Oliver J.T. J. Med. Chem. 26 (1983) 1158-1163
5. Tsuji K., and Ishikawa H. Bioorg. Med. Chem. Lett. 4 (1994) 1601-1606
6. Gorczynski M.J., Leal R.M., Mooberry S.L., Bushweller J.H., and Brown M.L. Bioorg. Med. Chem. Lett. 12 (2004) 1029-1036
7. Guba W., Neidhart W., and Nettekoven M. Bioorg. Med. Chem. Lett. 15 (2005) 1599-1603
8. Rajasekharan K.N., Nair K.P., and Jenardanan G.C. Synthesis (1986) 353-355
9. Sengupta S., Smitha S.L., Thomas N.E., Santhoshkumar T.R., Devi S.K.C., Sreejalekshmi K.G., and Rajasekharan K.N. Br. J. Pharmacol. 145 (2005) 1076-1083
10. Rosania G.R., and Chang Y.-T. Expert Opin. Ther. Patents 10 (2000) 215-230
11. Dorronsoro I., Castro A., and Martinez A. Expert Opin. Ther. Patents 12 (2002) 1527-1536
12. Katritzky A.R., Cai X., and Rogovoy B.V. J. Comb. Chem. 5 (2003) 392-399
13. Kazzouli S.E., Raboin S.B., Mouaddib A., and Guillaumet G. Tetrahedron Lett. 43 (2002) 3193-3196
14. Steiber F., Mazitschek R., Soric N., Giannis A., and Waldmann H. Angew. Chem., Int. Ed. 41 (2002) 4757-4761
15. Goff D., and Fernandez J. Tetrahedron Lett. 40 (1999) 423-426
16. Kearney P.C., Fernandez M., and Flygare J.A. J. Org. Chem. 63 (1998) 196-200
17. Baer R., and Masquelin T. J. Comb. Chem. 3 (2001) 16-19
18. Lee I.Y., Lee J.Y., Lee H.J., and Gong Y.-D. Synlett 16 (2005) 2483-2485
19. Jenardanan G.C., Francis M., Deepa S., and Rajasekharan K.N. Synth. Commun. 27 (1997) 3457-3462
20. 2/g by titrimetry.
21. Mathew B., and Pillai V.N.R. Eur. Polym. J. 30 (1994) 61-65
22. Solution phase pilot reactions on individual n-alkylamines with thiocarbamoyl transfer reagent 5a in acetonitrile at 50-55 °C afforded the corresponding 1-(N-alkylamidino)-3-phenylthioureas as major products in good yields.
23. 1 = alkyl) was used, the extent of thiocarbamoylamidine transfer was found to be low.
24. Each vessel was charged with 1.5 g of resin 8 swelled in acetonitrile (10 mL) followed by the thiocarbamoylamidine transfer reagent 5 (2 M equiv based on the amino group capacity of the resin) and kept at 70-75 °C for 12-15 h with occasional mixing. The suspension was then filtered while hot. The resin beads were washed in succession with the following warm solvents: acetonitrile (5 mL × 3); petroleum ether (2 mL × 3); acetonitrile (5 mL × 2); ethanol (95%, 5 mL × 3) and finally methanol (5 mL × 2). The resin was then dried under vacuum.
25. Devi S.K.C., and Rajasekharan K.N. Synth. Commun. 32 (2002) 1523-1528
26. To resin 9a (2.5 g, S capacity 0.8%), pre-swelled in DMF (10 mL), α-bromoketone 3a (1 M equiv) was added and the suspension was heated at 60 °C with occasional shaking for 30 min. After adding triethylamine (1.1 equiv) which acts as a catalyst as well as a quench for the generated HBr, the suspension was kept at 60 °C for another 30 min and then left at room temperature overnight. The resulting orange-yellow mixture was filtered and the resin beads were washed with DMF (2 mL × 2). The filtrate and washings were combined and slowly added to ice-water (75 mL) with rapid stirring. This afforded a yellow solid (86%). To obtain a pure sample for analysis, the crude product was purified on a silica gel (60-120 mesh) column using ethyl acetate-petroleum ether (3:1) mixture as eluent to obtain 1a (65%).
27. The crude product was analyzed by HPLC using a Shimadzu ODS column (25 cm × 4.6 mm) using a 1% TFA water-acetonitrile gradient.
28. The reuse of spent resin was explored by thoroughly washing it with a variety of solvents, drying and then taking it through the synthetic cycle as described above. As a typical example, thiazole 1b was obtained in 68% crude and 47% purified yield. Further repetition of the cycle deleteriously affected the yield and purity of the product.
29. Binu R., Thomas K.K., Jenardanan G.C., and Rajasekharan K.N. Org. Prep. Proced. Int. 30 (1998) 93-96
30. 3OS: C, 69.54; H, 4.38; N, 12.17. Found: C, 69.29; H, 4.62; N, 12.05.
31. 4OS: C, 58.61; H, 3.55; N, 15.19. Found: C, 58.56; H, 3.70; N, 15.28.
32. 3S: C, 57.36; H, 3.04; N, 10.56. Found: C, 57.20; H, 2.92; N, 10.62.