R. Mamouni et al. / Tetrahedron Letters 44 (2003) 2745–2747
2747
1
Figure 2. 400 MHz H NMR spectrum of 5a in DMSO-d6; NOE difference spectra resulting from irradiation of (a) NH proton,
(b) H6 and (c) H8.
In conclusion, this work presents a new synthesis of
pyrido[3,2-d]pyrimidine-2,4-diones 5 through a short
and efficient route, using 2,3-pyridinedicarboxylic acid
as inexpensive starting material. We are currently
exploring the construction of the other fused hetero-
cyclic systems with the aim to determine a common
pharmacophore.
Guillaumet, G.; Akssira, M. J. Heterocyclic Chem. 2000,
37, 1247 and references cited herein.
10. Aziane, D.; Soukri, M.; El Hakmaoui, A.; Lazar, S.;
Essassi, M.; Guillaumet, G.; Akssira, M. J. Heterocyclic
Chem. 2002, 39, 271.
11. Saoud, M.; Benabdelouahab, F. B.; El Guemmout, F.;
Romerosa, A. M. Heterocyclic Commun. 2001, 7, 5.
12. Kenyon, J.; Thaker, K. J. Chem. Soc. 1957, 2531.
13. Blanco, M. M.; Perillo, I. A.; Schapira, C. B. J. Hetero-
cyclic Chem. 1999, 36, 979.
Acknowledgements
14. Compound 5a: 1H NMR (DMSO-d6): l 4.59 (s, 2H,
CH2), 7.62–7.76 (m, 2H, HPy), 8.51–8.57 (m, 1H, HPy),
11.75 (s, 1H, NH), 13.1 (bs, 1H, COOH); MS: m/z 222
[M+1].
The authors would like to acknowledge the financial
support provided by the ministry ESRSFC of the
Moroccan Government (PROTARS P2T2/07) and Mr.
Haidour Ali from University of GRANADA, Spain
(Centro de Instrumentacio´n Cient´ıfica), for carrying out
NMR 2D experiences.
Compound 5b: 1H NMR (DMSO-d6): l 2.5 (t, 2H,
CH2COOH), 4.11 (t, 2H, CH2N), 7.50–7.70 (m, 2H, HPy),
8.40–8.60 (m, 1H, HPy), 11.53 (s, 1H, NH), 12.34 (bs, 1H,
COOH); MS: m/z 236 [M+1].
Compound 5c: 1H NMR (DMSO-d6): l 1.7 (d, 3H, CH3),
5.54 (q, 1H, CH), 7.40–7.58 (m, 2H, HPy), 8.60–8.70 (m,
1H, HPy); MS: m/z 236 [M+1].
References
Compound 5d: 1H NMR (DMSO-d6): l 1.48 (d, 3H,
CH3), 5.4 (q, 1H, CH), 7.50–7.80 (m, 2H, HPy), 8.40–8.60
(m, 1H, HPy), 11.65 (s, 1H, NH), 12.66 (bs, 1H, COOH);
MS: m/z 236 [M+1].
1. Hurlbert, B. S.; Valenti, B. F. J. Med. Chem. 1968, 11,
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Compound 5e: 1H NMR (DMSO-d6): l 3.35–3.56 (m,
2H, CH2), 5.68–80 (m, 1H, CH), 7.36–7.50 (m, 3H, HPh),
8.10–8.35 (m, 2H, HPy), 8.68–8.76 (m, 1H, HPy), 8.56 (s,
1H, NH); MS: m/z 312 [M+1].
4. Bornschein, L.; Kraft, R.; Pfeifer, S.; Ullmann, M.;
Longer, H. Pharmazie 1979, 34, 732.
Compound 5f: 1H NMR (DMSO-d6): l 6.70 (s, 1H,
CHPh), 7.49–7.60 (m, 3H, HPh), 7.93–8.20 (m, 2H, HPy),
8.58–8.62 (m, 1H, HPy), 10.65 (s, 1H, NH); MS: m/z 298
[M+1].
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D. V.; Yang, D.; Kelly, K.; Eglen, R. M. Can. J. Physiol.
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Compound 5g: 1H NMR (D2O):
CH2CH2COOH, J=6.40 Hz),
l
3.02 (dd, 2H,
3.36 (dt, 2H,
CH2CH2COOH, J=7.72 Hz), 5.80 (dd, 1H, CH, J=
6.97), 7.98–8.15 (m, 2H, HPy), 8.20–8.35 (m, 1H, HPy),
8.65 (s, 1H, NH); MS: m/z 294 [M+1].
15. Lin, L.-Z.; Lin, L.-J.; Cordell, G. A.; Luo, S.-Q.; Jiang,
H.-F. Magn. Res. Chem. 1992, 30, 1097 and references
cited therein.
8. Akssira, M.; Dahdouh, A.; Kasmi, H.; Boumzebra, M.;
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9. El Haddad, M.; Soukri, M.; Lazar, S.; Bennamara, A.;