A convenient synthesis of trisubstituted pyrido[2,3-d]pyrimidin-7-ones

Tetrahedron Letters

Volumn 44, Issue 24, 2003, Pages 4567-4570

  Kasparec, Jiri ^a   Adams, Jerry L ^a   Sisko, Joseph ^a   Silva, Domingos J ^a  

^a GLAXOSMITHKLINE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

KETONE DERIVATIVE;

ARTICLE; HORNER WADSWORTH EMMONS REACTION; MOLECULAR BIOLOGY; OXIDATION; POLYMERIZATION; SYNTHESIS;

EID: 0037727911     PISSN: 00404039     EISSN: None     Source Type: Journal    
DOI: 10.1016/S0040-4039(03)00974-2     Document Type: Article

References (14)

1. Barvian M., Boschelli D.H., Cossrow J., Dobrusin E., Fattaey A., Fritsch A., Fry D., Harvey P., Keller P., Garrett M., La F., Leopold W., McNamara D., Quin M., Trumpp-Kallmeyer S., Toogood P., Wu Z., Zhang E. J. Med. Chem. 43:2000;4606-4616.
2. Klutchko S.R., Hamby J.M., Boschelli D.H., Wu Z., Kraker A.J., Amar A.M., Hartl B.G., Shen C., Klohs W.D., Steinkampf R.W., Driscoll D.L., Nelson J.M., Elliott W.L., Roberts B.J., Stoner C.L., Vincent P.W., Dykes D.J., Panek R.L., Lu G.H., Major T.C., Dahring T.K., Hallak H., Bradford L.A., Showalter H.D.H., Doherty A.M. J. Med. Chem. 41:1998;3276-3292.
3. Boschelli D.H., Wu Z., Klutchko S.R., Showalter H.D.H., Hamby J.M., Lu G.H., Major T.C., Dahring T.K., Batley B., Panek R.L., Keiser J., Hartl B.G., Kraker A.J., Klohs W.D., Roberts B.J., Patmore S., Elliott W.L., Steinkampf R., Bradford L.A., Hallak H., Doherty M. J. Med. Chem. 41:1998;4365-4377.
4. Aldehyde 5 is available from Maybridge but may also be easily prepared in one step from the more readily available 4,6-dihydroxy-2-methylsulfanylpyrimidine using the procedure described in: (a) Santilli, A. A.; Dong, H. K.; Wander, S. K. J. Heterocyclic Chem. 1971, 8, 445-453. For other examples of previously described pyrimidines which could be used to assemble a heavily derivatized bicyclic system, see: (b) Taylor, E. C.; Gillespie, P. J. Org. Chem. 1992, 57, 5757-5761; (c) Wormstadt, F.; Brinckman, U.; Gutschow, M.; Eger, K. J. Heterocyclic Chem. 2000, 37, 1187-1191.
5. Aldehyde 5 is available from Maybridge but may also be easily prepared in one step from the more readily available 4,6-dihydroxy-2-methylsulfanylpyrimidine using the procedure described in: (a) Santilli, A. A.; Dong, H. K.; Wander, S. K. J. Heterocyclic Chem. 1971, 8, 445-453. For other examples of previously described pyrimidines which could be used to assemble a heavily derivatized bicyclic system, see: (b) Taylor, E. C.; Gillespie, P. J. Org. Chem. 1992, 57, 5757-5761; (c) Wormstadt, F.; Brinckman, U.; Gutschow, M.; Eger, K. J. Heterocyclic Chem. 2000, 37, 1187-1191.
6. Aldehyde 5 is available from Maybridge but may also be easily prepared in one step from the more readily available 4,6-dihydroxy-2-methylsulfanylpyrimidine using the procedure described in: (a) Santilli, A. A.; Dong, H. K.; Wander, S. K. J. Heterocyclic Chem. 1971, 8, 445-453. For other examples of previously described pyrimidines which could be used to assemble a heavily derivatized bicyclic system, see: (b) Taylor, E. C.; Gillespie, P. J. Org. Chem. 1992, 57, 5757-5761; (c) Wormstadt, F.; Brinckman, U.; Gutschow, M.; Eger, K. J. Heterocyclic Chem. 2000, 37, 1187-1191.
7. Still W.C., Gennari C. Tetrahedron Lett. 24:1983;4405-4408.
8. Jacobsen E.N., Deng L., Furukawa Y., Martinez L.E. Tetrahedron. 50:1994;4323-4334.
9. 3): δ 2.55 (s, 3H), 7.17 (m, 1H), 7.29 (m, 2H), 7.44 (m, 1H), 10.37 (s, 1H), 11.49 (br s, 1H). LC MS (m/e)=315 (MH+).
10. 3): δ 2.58 (s, 3H), 7.01-7.59 (m, 7H), 8.61 (d, 1H, J=4.7 Hz), 9.65 (s, 1H), 11.48 (br s, 1H). LC MS (m/e)=390 (MH+).
11. 3): δ 1.99 (s, 3H), 6.50 (d, 1H, J=9.7 Hz), 7.11-7.48 (m, 9H). LC MS (m/e)=414 (MH+).
12. Matyus P., Lowinger L., Wamhoff H. Heterocycles. 23:1985;2057-2064.
13. 3): δ 3.15 (s, 3H), 6.96 (d, 1H, J=9.8 Hz), 7.26 (m, 2H), 7.51-7.80 (m, 9H). LC MS (m/e)=446 (MH+).
14. 3): δ 2.59 (m, 2H), 3.11 (m, 2H), 5.91 (br s, 1H), 6.40 (d, 1H, J=9.6 Hz), 7.25-7.61 (m, 9H). LC MS (m/e)=426 (MH+).