Synthesis of pyrido[2,3-d]pyrimidines via palladium-catalyzed reaction of iodouracil with acetylenes

Tetrahedron Letters

Volumn 41, Issue 31, 2000, Pages 5899-5902

  Bae, Jong Woo ^a   Lee, Seung Hwan ^a   Cho, Young Jin ^a   Jung, Yeon Joo ^a   Hwang, Han June ^a   Yoon, Cheol Min ^a  

^a Korea University   (South Korea)

Author keywords

Acetylene; Iodouracil; LiCl; Palladium acetate; Pyridopyrimidine

Indexed keywords

ACETYLENE; PYRIMIDINE DERIVATIVE; URACIL DERIVATIVE;

ARTICLE; CATALYSIS; CHEMICAL REACTION; REACTION ANALYSIS; SYNTHESIS; THIN LAYER CHROMATOGRAPHY;

EID: 0000262683     PISSN: 00404039     EISSN: None     Source Type: Journal    
DOI: 10.1016/S0040-4039(00)00964-3     Document Type: Article

References (17)

1. (a) Larock, R. C.; Yum, E. K. J. Am. Chem. Soc. 1991, 113, 6689.
2. (b) Larock, R. C.; Doty, M. J.; Cacchi, S. J. J. Org. Chem. 1993, 58, 4579.
3. (c) Larock, R. C.; Yum, E. K.; Doty, M. J.; Sham, K. K. C. J. Org. Chem. 1995, 60, 3270.
4. (d) Larock, R. C.; Doty, M. J.; Tian, Q.; Zenner, J. M. J. Org. Chem. 1997, 62, 7536.
5. (e) Larock, R. C.; Han, X.; Doty, M. J. Tetrahedron Lett. 1998, 39, 5713.
6. (f) Ujjainwalla, F.; Warner, D. Tetrahedron Lett. 1998, 39, 5355.
7. (g) Quan, L. G.; Gevorgyan, V.; Yamamoto, Y. J. Am. Chem. Soc. 1999, 121, 3545.
8. (h) Larksarp, C.; Alper, H. J. Org. Chem. 1999, 64, 9194.
9. (i) Radhakrishnan, K. V.; Yoshikawa, E.; Yamamoto, Y. Tetrahedron Lett. 1999, 40, 7533.
10. (a) Grivsky, E. M.; Lee, S.; Siegel, C. W.; Nichol, C. A. J. Med. Chem. 1980, 23, 327.
11. (b) Rahman, L. K. A.; Chhabra, S. R. Med. Res. Rev. 1988, 8, 95.
12. Rho, K. Y.; Kim, J. H.; Kim, S. H.; Yoon, C. M. Heterocycles 1998, 12, 2521.
13. Rho, Y. H.; Bae, J. W.; Nam, G. S.; Kim, J. H.; Kim, S. H.; Yoon, C. M. Synth. Commun. 2000, 30, 81.
14. One equivalent of lithium chloride in the reaction was identified to be the optimal amount for the selectivity. When 2 equiv. of lithium chloride was used, several other side products were observed by TLC. When 0.5 equiv. of lithium chloride was used, the selectivity was decreased. In this case, 14% of deaminated product 3a was obtained.
15. The reaction of iodouracil 1a with 1-phenyl-1-propyne 2b in the absence of lithium chloride resulted in less selectivity, as shown below.
16. 2 bond in the absence of lithium chloride is possible to form intermediate II (Scheme 2).
17. 3 (82 mg, 0.595 mmol), lithium chloride (12.6 mg, 0.297 mmol) and diphenylacetylene (80 mg, 0.446 mmol). The resulting solution was stirred at 120°C for 1.5 h under nitrogen, concentrated under reduced pressure and chromatographed on silica gel using a solution of ethyl acetate:hexane (1:10). Eluent concentration gave two pyrido[2,3-d]pyrimidines as a white solid.