N. R. Mohamed et al. / Bioorg. Med. Chem. 15 (2007) 6227–6235
6233
3.45%; N, 11.08%; S, 8.45%. Found: C, 60.04%; H,
3.32%; N, 10.93%; S, 8.37%.
for 4 h. The solvent was evaporated under vacuum.
The solid product formed after washing the remaining
residue with n-hexane was collected by filtration and
crystallized from dioxane.
4.2.1.5. 5-(Naphthalene-2-carbonyl)-7-phenyl-2-thi-
oxo-2,3-dihydro-1H-pyrido[2,3-d]pyrimidin-4-one (8e).
Yield 3.5 g (86%); yellow crystals; mp 233 °C; IR
(KBr, cmÀ1): 3399 (NH), 1643 (C@O), 1630 (C@O),
1178 (C@S); 1H NMR: d (ppm) = 6.70–7.25 (m, 5H,
aromatic protons), 7.30 (s, 1H, H-6), 7.54–8.02 (m,
6H, naphthyl protons), 8.50 (s, 1H, naphthyl proton),
11.85 (s, 1H, NH), 12.10 (s, 1H, NH); MS (m/z) = 409
(M+, 43.3%). Anal. Calcd for C24H15N3O2S: C,
70.40%; H, 3.69%; N, 10.26%; S, 7.83%. Found: C,
70.33%; H, 3.57%; N, 10.13%; S, 7.79%.
4.3.1.1. Diethyl 4-oxo-7-phenyl-2-thioxo-1,2,3,4-tetra-
hydro-pyrido[2,3-d]pyrimidine-5,6-dicarboxylate (13a).
Yield 3.5 g (87%); orange crystals; mp 235 °C; IR
(KBr, cmÀ1): 3419 (NH), 1760 (C@O), 1726 (C@O),
1
1633 (C@O), 1182 (C@S); H NMR: d (ppm) = 1.13–
1.29 (m, 6H, 2CH3), 4.13–4.28 (m, 4H, 2CH2), 6.77–
7.21 (m, 5H, aromatic protons), 11.85 (s, 1H, NH),
12.05 (s, 1H, NH). 13C NMR: d (ppm) = 14.02, 14.50
(2CH3), 62.49, 66.87 (2CH2), 109.40, 119.10, 126.89,
127.07, 127.90, 128.29, 142.0, 156.0, 161.53, 163.0
(C@O), 166.01 (C@O), 166.80 (C@O), 172.90 (C@S);
MS (m/z) = 399 (M+, 9.6%), 354 (M+ÀOEt, 9.6%).
Anal. Calcd for C19H17N3O5S: C, 57.13%; H, 4.29%;
N, 10.52%; S, 8.03%. Found: C, 57.04%; H, 4.23%; N,
10.43%; S, 7.9%.
4.2.1.6. 7-(4-Methoxy-phenyl)-5-(naphthalene-2-car-
bonyl)-2-thioxo-2,3-dihydro-1H-pyrido[2,3-d]pyrimidin-4-
one (8f). Yield 3.8 g (87%); yellow crystals; mp 248 °C;
IR (KBr, cmÀ1): 3408 (NH), 1646 (C@O), 1628
1
(C@O), 1175 (C@S); H NMR: d (ppm) = 3.55 (s, 3H,
OCH3), 6.75 (d, 2H, aromatic protons, J = 7.5 Hz),
6.94 (d, 2H, aromatic protons, J = 7.5 Hz), 7.55 (s,
1H, H-6), 7.56–8.05 (m, 6H, naphthyl protons), 8.50
(s, 1H, naphthyl protons), 11.85 (s, 1H, NH), 12.04 (s,
1H, NH); MS (m/z) = 439 (M+, 27.9%). Anal. Calcd
for C25H17N3O3S: C, 68.32%; H, 3.90%; N, 9.56%; S,
7.30%. Found: C, 68.21%; H, 3.85%; N, 9.47%; S,
7.23%.
4.3.1.2. Diethyl 7-(4-methoxyphenyl)-4-oxo-2-thioxo-
1,2,3,4-tetrahydropyrido[2,3-d]pyrimidine-5,6-dicarboxy-
late (13b). Yield 3.8 g (88%); orange crystals; mp 246 °C;
IR (KBr, cmÀ1): 3426 (NH), 1762 (C@O), 1733 (C@O),
1
1637 (C@O), 1180 (C@S); H NMR: d (ppm) = 1.13–
1.29 (m, 6H, 2CH3), 3.69 (s, 3H, OCH3), 4.13–4.45 (m,
4H, 2CH2), 6.77–6.98 (m, 4H, aromatic protons),
11.82 (s, 1H, NH), 12.01 (s, 1H, NH); MS (m/z) = 429
(M+, 3.0%), 384 (M+ÀOEt, 61.0%). Anal. Calcd for
C20H19N3O6S: C, 55.94%; H, 4.46%; N, 9.78%; S,
7.47%. Found: C, 55.86%; H, 4.34%; N, 9.69%; S,
7.36%.
4.2.1.7. 4-Oxo-7-phenyl-2-thioxo-1,2,3,4-tetrahydro-
pyrido[2,3-d]pyrimidine-5-carbonitrile (11a). Yield 1.9 g
(70%); brown crystals; mp 213 °C; IR (KBr, cmÀ1):
1
3398 (NH), 2203 (CN), 1643 (C@O), 1178 (C@S); H
NMR: d (ppm) = 6.80–7.40 (m, 5H, aromatic protons),
7.38 (s, 1H, H-6), 11.83 (s, 1H, NH), 12.06 (s, 1H,
NH); MS (m/z) = 280 (M+, 7.0%). Anal. Calcd for
C14H8N4OS: C, 59.99%; H, 2.88%; N, 19.99%; S,
11.44%. Found: C, 59.87%; H, 2.75%; N, 19.87%; S,
11.38%.
4.3.1.3. Dimethyl 4-oxo-7-phenyl-2-thioxo-1,2,3,4-tet-
rahydro-pyrido[2,3-d]pyrimidine-5,6-dicarboxylate (13c).
Yield 3.2 g (86%); yellow crystals; mp 200 °C; IR (KBr,
cmÀ1) 3426 (NH), 1762 (C@O), 1732 (C@O), 1636
1
(C@O), 1184 (C@S); H NMR: d (ppm) = 3.72 (s, 3H,
CH3), 3.79 (s, 3H, CH3), 7.01–7.38 (m, 5H, aromatic
protons), 11.80 (s, 1H, NH), 12.05 (s, 1H, NH); MS
(m/z) = 371 (M+, 2.5%), 356 (M+ÀMe, 3.4%). Anal.
Calcd for C17H13N3O5S: C, 54.98%; H, 3.53%; N,
11.31%; S, 8.63%. Found: C, 54.87%; H, 3.44%; N,
11.27%; S, 8.57%.
4.2.1.8. 7-(4-Methoxy-phenyl)-4-oxo-2-thioxo-1,2,3,4-
tetrahydro-pyrido[2,3-d]pyrimidine-5-carbonitrile (11b).
Yield 2.3 g (76%); brown crystals; mp 228 °C; IR
(KBr, cmÀ1): 3401 (NH), 2182 (CN), 1649 (C@O),
1174 (C@S); 1H NMR:
d (ppm) = 3.55 (s, 3H,
OCH3), 6.75 (d, 2H, aromatic protons, J = 7.5 Hz),
6.94 (d, 2H, aromatic protons, J = 7.5 Hz), 7.35 (s,
1H, H-6), 11.83 (s, 1H, NH), 12.06 (s, 1H, NH);
4.3.1.4. Dimethyl 7-(4-methoxyphenyl)-4-oxo-2-thi-
oxo-1,2,3,4-tetrahydropyrido[2,3-d]pyrimidine-5,6-dicarb-
oxylate (13d). Yield 3.6 g (89%); yellow crystals; mp
220 °C; IR (KBr, cmÀ1): 3425 (NH), 1763 (C@O),
13C NMR (DMSO-d6):
d (ppm) = 55.52 (OCH3),
90.42, 91.12, 113.70, 113.84 (CN), 128.05, 128.82,
130.21, 142.0, 153.96, 157.69, 163.50 (C@O), 173.37
(C@S); MS (m/z) = 310 (M+, 8.8%). Anal. Calcd for
C15H10N4O2S: C, 58.06%; H, 3.25%; N, 18.05%; S,
10.33%. Found: C, 57.92%; H, 3.12%; N, 17.96%; S,
10.24%.
1
1733 (C@O), 1642 (C@O), 1181 (C@S); H NMR: d
(ppm) = 3.58 (s, 3H, OCH3), 3.72 (s, 3H, CH3), 3.84
(s, 3H, CH3), 7.01–7.38 (m, 4H, aromatic protons),
11.85 (s, 1H, NH), 12.05 (s, 1H, NH); MS (m/z) = 401
(M+, 2.1%), 386 (M+ÀMe, 20.8%). Anal. Calcd for
C18H15N3O6S: C, 53.86%; H, 3.77%; N, 10.47%; S,
7.99%. Found: C, 53.79%; H, 3.63%; N, 10.34%; S,
7.82%.
4.3. Cycloaddition reaction of 2-azadiene 3a,b with
acetylenes
4.3.1. General procedure. To a solution of each of 2-
azadiene 3a,b (0.01 mol) in dry dioxane (30 ml), equimo-
lar amounts of one of the acetylenes 12a,b or 14 was
added. The reaction mixture was heated under reflux
4.3.1.5. Ethyl 4-oxo-7-phenyl-2-thioxo-1,2,3,4-tetrahy-
dro-pyrido[2,3-d]pyrimidine-5-carboxylate (16a). Yield
2.65 g (81%); yellow crystals; mp 242 °C; IR (KBr,
cmÀ1): 3407 (NH), 1761 (C@O), 1644 (C@O), 1173