A facile reduction of 2-aminopyrimidines with triethylsilane and trifluoroacetic acid

Tetrahedron Letters

Volumn 45, Issue 10, 2004, Pages 2107-2111

  Baskaran, Subramanian ^a   Hanan, Emily ^a   Byun, Daniel ^a   Shen, Wang ^a  

^a Sunesis Pharmaceuticals Inc   (United States)

Author keywords

Guanidine; Pyrimidine; Reduction; Triethylsilane

Indexed keywords

2 AMINOPYRIDINE DERIVATIVE; SILANE DERIVATIVE; TRIFLUOROACETIC ACID;

ARTICLE; REDUCTION; TEMPERATURE;

EID: 1242340505     PISSN: 00404039     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.tetlet.2004.01.056     Document Type: Article

References (14)

1. Recent biological applications of 2-amino-3,4,5,6-tetrahydropyrimidines: Perron-Sierra F., Saint Dizier D., Bertrand M., Genton A., Tucker G.C., Casara P. Bioorg. Med. Chem. Lett. 12:2002;3291.
2. Reiner J.E., Siev D.V., Araldi G.-L., Cui J.J., Ho J., Reddy K.M., Mamedova L., Vu P.H., Lee K.-S.S., Minami N.K., Gibson T.S., Anderson S.M., Bradbury A.E., Nolan T.G., Semple J.E. Bioorg. Med. Chem. Lett. 12:2002;1203.
3. Batt D.G., Petraitis J.J., Houghton G.C., Modi D.P., Cain G.A., Corjay M.H., Mousa S.A., Bouchard P.J., Forsynthe M.S., Harlow P.P., Barbera F.A., Spitz S.M., Wexler R.R., Jadhav P.K. J. Med. Chem. 43:2000;41.
4. Biological application of 2-amino-5,6-dihydropyrimidines: Cho H., Ueda M., Shima K., Mizuno A., Hayashimatsu M., Ohnaka Y., Takeuchi Y., Hamaguchi M., Aisaka K., Hidaka T., Kawai M., Takeda M., Ishihara T., Funahashi K., Satoh F., Morita M., Noguchi T. J. Med. Chem. 32:1989;2399.
5. Duggan M.E., Duong L.T., Fisher J.E., Hamill T.G., Hoffman W.F., Huff J.R., Ihle N.C., Leu C.-T., Nagy R.M., Perkins J.T., Rodan S.B., Wesolowski G., Whitman D.B., Zartman A.E., Rodan G.A., Hartman G.D. J. Med. Chem. 43:2000;3736.
6. 2-Amino-3,4-dihydropyrimidines are prepared by Michael addition of guanidine and subsequent condensation, see Reference 2 and Kahsima C., Shimizu M., Omote Y. J. Heterocycl. Chem. 26:1989;251.
7. Vargo L., Nagy T., Kovesdi I., Benet-Buchholz J., Dorman G., Uerge L., Darvas F. Tetrahedron. 59:2003;655.
8. SM is a service mark of Sunesis Pharmaceuticals Inc. for its fragment-based drug discovery.
9. Pyrimidines 1 , 3 starting pyrimidines in Table 2 (entries 1 and 2) are synthesized by Suzuki coupling from the corresponding 2-amino-5-bromo(or chloro)pyrimidines. Pyridine 14 was synthesized in a similar manner.
10. The intended 2-amino-pyrimidine derivative was obtained at 40-60% yield if anisole is used instead of triethylsilane in TFA, or by using 4.0 M HCl in dioxane.
11. Triethylsilane as reducing reagent, a review: Fry J.L. Burke S.D., Danheiser R.L. Handbook of Reagents for Organic Synthesis: Oxidizing and Reducing Agents. 1999;479 Wiley-VCH, Chichester.
12. Aurelio L., Box J.S., Brownlee R.T.C., Hughes A.B., Sleebs M.M. J. Org. Chem. 68:2003;2652.
13. Olivo H.F., Colby D.A., Hemenway M.S. J. Org. Chem. 64:1999;4966.
14. Monitoring the reactions with LC-MS revealed that 2- aminodihydropyrimidines always appeared concurrently with significant amounts of starting material and further reduced 2-aminotetrahydropyrimidines.